Gene Detail

Gene Symbol FLT3
Synonyms CD135 | FLK-2 | FLK2 | STK1
Gene Description FLT3, receptor-type tyrosine-protein kinase FLT3, activates Akt, Ras, and Erk pathways to regulate differentiation, proliferation, and survival of hematopoietic progenitor cells (PMID: 29316714, PMID: 28538663). Activating mutations of FLT3 are common in hematologic tumors (PMID: 19467916) and the internal tandem duplication (ITD) mutation is commonly observed in acute myeloid leukemia (PMID: 30181385).
Entrez Id 2322
Chromosome 13
Map Location 13q12.2
Canonical Transcript NM_004119

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
D835F missense unknown FLT3 D835F lies within the protein kinase domain activation loop of the Flt3 protein (PMID: 11290608). D835F has been associated with acquired resistance to sorafenib (PMID: 24227820), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Oct 2018). Y
F594_D600dup duplication gain of function - predicted FLT3 F594_D600dup indicates the insertion of 7 duplicate amino acids, phenylalanine (F)-594 through aspartic acid (D)-600, in the juxtamembrane domain of the Flt3 protein (PMID: 14759363). F594_D600dup has not been biochemically characterized, but can be predicted to lead to activation of Flt3 based on the effects of other Flt3 internal tandem duplication (ITD) mutations (PMID: 12970773, PMID: 9737679, PMID: 11090077).
V592G missense gain of function FLT3 V592G lies within the protein kinase domain of the Flt3 protein (UniProt.org). V592G results in constitutive phosphorylation of Flt3, activation of Stat3/5, Akt, and Erk signaling, and is transforming in culture (PMID: 18068628).
Y597_K602dup duplication gain of function - predicted FLT3 Y597_K602dup indicates the insertion of 6 duplicate amino acids, tyrosine (Y)-597 through lysine (K)-602, in the juxtamembrane domain of the Flt3 protein (PMID: 14759363). Y597_K602dup has not been biochemically characterized, but can be predicted to lead to activation of Flt3 based on the effects of other Flt3 internal tandem duplication (ITD) mutations (PMID: 12970773, PMID: 9737679, PMID: 11090077).
exon 14 ins insertion gain of function - predicted FLT3 exon 14 ins refers to a series of internal tandem duplications (ITD) typically occurring in exon 14 and within the juxtamembrane domain of the Flt3 protein (PMID: 12970773). Exon 14 ins mutations often result in constitutive activation of Flt3 (PMID: 12970773) and therefore, is predicted to lead to a gain of Flt3 protein function.
V819I missense unknown FLT3 V819I lies within the protein kinase domain of the Flt3 protein (UniProt.org). V819I has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
W603_E604insDREYEYDLKW insertion gain of function - predicted FLT3 W603_E604insDREYEYDLKW results in the insertion of ten amino acids in the juxtamembrane domain of the Flt3 protein between amino acids 603 and 604 (UniProt.org). W603_E604insDREYEYDLKW has not been biochemically characterized, but can be predicted to lead to activation of Flt3 based on the effects of other Flt3 internal tandem duplication (ITD) mutations (PMID: 12970773, PMID: 9737679, PMID: 11090077).
mutant unknown unknown FLT3 mutant indicates an unspecified mutation in the FLT3 gene.
F691L missense unknown FLT3 F691L lies within the protein kinase domain of the Flt3 protein (PMID: 23430109). F691L has been demonstrated to promote secondary drug resistance in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 23430109, PMID: 19318574; PMID: 22504184, PMID: 29187377), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Jun 2018). Y
T136N missense unknown FLT3 T136N lies within the extracellular domain of the Flt3 protein (UniProt.org). T136N has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Oct 2018).
S838R missense unknown FLT3 S838R lies within the protein kinase domain of the Flt3 protein (UniProt.org). S838R has been demonstrated to confer drug resistance when in the context of FLT3 internal tandem duplication (FLT3-ITD) compound mutations co-occurring in tandem M837G and D839H (PMID: 25847190), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Jun 2018). Y
G822R missense unknown FLT3 G822R lies within the protein kinase domain of the Flt3 protein (UniProt.org). G822R has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
N841I missense gain of function FLT3 N841I lies within the protein kinase domain of the Flt3 protein (UniProt.org). N841I results in constitutive phosphorylation of Flt3, activation of Akt and Mapk signalling pathways, leading to leukemogenicity in animal models (PMID: 15178581).
V194M missense no effect - predicted FLT3 V194M lies within the extracellular domain of the Flt3 protein (UniProt.org). V194M does not result in IL-3 independent growth of cultured cells in one study (PMID: 18068628) and therefore, is predicted to have no effect on Flt3 protein function.
S840_N841insGS insertion gain of function FLT3 S840_N841insGS results in the insertion of two amino acids in the protein kinase domain of the Flt3 protein between amino acids 840 and 841 (UniProt.org). S840_N841insGS results in constitutive phosphorylation Flt3 and transformation of cultured cells (PMID: 12384447).
F590_Y591delinsGD indel gain of function FLT3 F590_Y591delinsGD results in a deletion of 2 amino acids in the juxtamembrane domain of the Flt3 protein from amino acids 590 to 591, combined with the insertion of a glycine (G) and an aspartic acid (D) at the same site (PMID: 11756186). F590_Y591delinsGD results in constitutive phosphorylation of Flt3, activation of Stat5 signaling, and transformation of cells in culture (PMID: 16410449).
Y599_D600insEYEYEYEY insertion gain of function - predicted FLT3 Y599_D600insEYEYEYEY results in the insertion of eight amino acids in the juxtamembrane domain of the Flt3 protein between amino acids 599 and 600 (UniProt.org). Y599_D600insEYEYEYEY has not been biochemically characterized, but can be predicted to lead to activation of Flt3 based on the effects of other Flt3 internal tandem duplication (ITD) mutations (PMID: 12970773, PMID: 9737679, PMID: 11090077).
F594Y missense gain of function FLT3 F594Y lies within the juxtamembrane domain of the Flt3 protein (PMID: 29164965). F594Y results in increased phosphorylation of Ftt3 and Stat5 in culture (EHA, June 2017, abstr P184).
L611_E612insCSSDNEYFYVDFREYEYDLKWEFPRENL insertion gain of function FLT3 L611_E612insCSSDNEYFYVDFREYEYDLKWEFPRENL results in the insertion of 28 amino acids in the cytoplasmic juxtamembrane region of the Flt3 protein between amino acids L611 and E612 (UniProt.org, PMID: 11756186). L611_E612insCSSDNEYFYVDFREYEYDLKWEFPRENL results in constitutive phosphorylation of Flt3, activation of Stat5 and Mapk signaling, and transformation of cultured cells (PMID: 10698507, PMID: 11756186).
S985fs frameshift unknown FLT3 S985fs results in a change in the amino acid sequence of the Flt3 protein beginning at aa 895 of 933, likely resulting in premature truncation of the functional protein (UniProt.org). S985fs has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Oct 2018).
F621L missense unknown FLT3 F621L lies within the protein kinase domain of the Flt3 protein (UniProt.org). F621L has been identified in the scientific literature (Blood 2009 114:3776), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Oct 2018).
V557A missense unknown FLT3 V557A lies within the helical domain of the Flt3 protein (UniProt.org). V557A has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
R607fs frameshift loss of function - predicted FLT3 R607fs results in a change in the amino acid sequence of the Flt3 protein beginning at aa 607 of 993, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), R607fs is predicted to lead to a loss of function.
E77K missense unknown FLT3 E77K lies within the extracellular domain of the Flt3 protein (UniProt.org). E77K has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
D835Y missense gain of function FLT3 D835Y lies within the protein kinase domain activation loop of the Flt3 protein (UniProt.org, PMID: 11290608). D835Y results in constitutive phosphorylation of Flt3 and activation of Stat5, Erk signaling, leading to transformation of cultured cells (PMID: 15256420), and has been demonstrated to promote secondary drug resistance in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 22504184, PMID: 29187377). Y
E598_Y599insGLVQVTGSSDNEYFYVDFREYE insertion gain of function FLT3 E598_Y599insGLVQVTGSSDNEYFYVDFREYE results in the insertion of 22 amino acids in the cytoplasmic juxtamembrane region of the Flt3 protein between amino acids E598 and Y599 (PMID: 11756186). E598_Y599insGLVQVTGSSDNEYFYVDFREYE confers a gain of function on Flt3 protein as indicated by transformation of cells in culture and induction of myeloproliferative disorder in mouse models (PMID: 11756186).
M664I missense unknown FLT3 M664I lies within the protein kinase domain of the Flt3 protein (UniProt.org). M664I has been demonstrated to occur as a secondary resistance mutation in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 25847190), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Jun 2018). Y
D7G missense unknown FLT3 D7G does not lie within any known functional domains of the Flt3 protein (UniProt.org). D7G has been identified in the scientific literature (PMID: 27350795), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Sep 2018).
D835del deletion gain of function FLT3 D835del results in the deletion of an amino acid in the protein kinase domain activation loop of the Flt3 protein at amino acid 835 (UniProt.org, PMID: 11290608). D835del results in constitutive phosphorylation of Flt3 and activation of Stat5, Erk signaling, leading to transformation of cultured cells (PMID: 15256420).
A450E missense unknown FLT3 A450E lies within the extracellular domain of the Flt3 protein (UniProt.org). A450E has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Sep 2018).
amp none no effect FLT3 amplification indicates an increased number of copies of the FLT3 gene. However, the mechanism causing the increase is unspecified.
positive unknown unknown FLT3 positive indicates the presence of the FLT3 gene, mRNA, and/or protein.
R933L missense unknown FLT3 R933L lies within the protein kinase domain of the Flt3 protein (UniProt.org). R933L has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Oct 2018).
F804C missense unknown FLT3 F804C lies within the protein kinase domain of the Flt3 protein (UniProt.org). F804C has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
K438fs frameshift loss of function - predicted FLT3 K438fs results in a change in the amino acid sequence of the Flt3 protein beginning at aa 438 of 993, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), K438fs is predicted to lead to a loss of function.
V557I missense unknown FLT3 V557I lies within the transmembrane domain of the Flt3 protein (PMID: 18068628). V557I has been identified in the scientific literature (PMID: 18068628), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Oct 2018).
A680V missense gain of function - predicted FLT3 A680V lies within the N-terminal kinase domain of the Flt3 protein (PMID: 15976757). A680V results in autophosphorylation of Flt3 in culture in one study (ASH, 2015, abstract no. 87) and therefore, is predicted to lead to a gain of Flt3 protein function.
D839A missense unknown FLT3 D839A lies within the activation loop of the protein kinase domain of the Flt3 protein (UniProt.org). D839A has been demonstrated to occur as a secondary resistance mutation in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 25847190), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Jun 2018). Y
L832F missense unknown FLT3 L832F lies within the protein kinase domain of the Flt3 protein (UniProt.org). L832F has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
F594C missense gain of function FLT3 F594C lies within the juxtamembrane domain of the Flt3 protein (PMID: 29164965). F594C results in increased phosphorylation of Ftl3 and Stat5 in culture (EHA, June 2017, abstr P184).
P738R missense unknown FLT3 P738R lies within the protein kinase domain of the Flt3 protein (UniProt.org). P738R has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
Y842C missense gain of function FLT3 Y842C lies within the protein kinase domain of the Flt3 protein (UniProt.org). Y842C results in constitutive phosphorylation of Flt3, activation of Stat5 signaling, is transforming in cell culture (PMID: 15345593), and has been demonstrated to promote secondary drug resistance in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 22504184, PMID: 29187377). Y
F590G missense unknown FLT3 F590G does not lie within any known functional domains of the Flt3 protein (UniProt.org). F590G has been identified in sequencing studies (PMID: 14984498) but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Oct 2018).
T820A missense unknown FLT3 T820A lies within the protein kinase domain of the Flt3 protein (UniProt.org). T820A has been demonstrated to occur as a secondary resistance mutation in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 25847190), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Jun 2018). Y
M737I missense no effect - predicted FLT3 M737I lies within the protein kinase domain of the Flt3 protein (UniProt.org). M737I does not result in IL-3 independent growth of cultured cells in one study (PMID: 18068628) and therefore, is predicted to have no effect on Flt3 protein function.
G282R missense unknown FLT3 G282R lies within the Ig-like C2-type domain of the Flt3 protein (UniProt.org). G282R has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Oct 2018).
S451F missense gain of function FLT3 S451F lies within the extracellular domain of the Flt3 protein (UniProt.org). S541F results in constitutive phosphorylation of Flt3, activation of Erk signaling, and is transforming in culture (PMID: 18068628).
D835H missense gain of function FLT3 D835H lies within the protein kinase domain activation loop of the Flt3 protein (UniProt.org, PMID: 11290608). D835H results in constitutive phosphorylation of Flt3 and activation of Stat5, Erk signaling, leading to transformation of cultured cells (PMID: 15256420).
S71I missense unknown FLT3 S71I lies within the protein kinase domain of the Flt3 protein (UniProt.org). S71I has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
I836M missense unknown FLT3 I836M lies within the protein kinase domain of the Flt3 protein (UniProt.org). I836M has been identified in sequencing studies (PMID: 15390271), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
N676T missense unknown FLT3 N676T lies within the protein kinase domain of the Flt3 protein (UniProt.org). N676T has been identified in sequencing studies (PMID: 27276561), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Jun 2018).
V197A missense unknown FLT3 V197A lies within the extracellular domain of the Flt3 protein (UniProt.org). V197A has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Oct 2018).
E708G missense unknown FLT3 E708G lies within the protein kinase domain of the Flt3 protein (UniProt.org). E708G has been identified in sequencing studies (PMID: 25847190), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
D870E missense unknown FLT3 D870E lies within the protein kinase domain of the Flt3 protein (UniProt.org). D870E has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
D839N missense unknown FLT3 D839N lies within the activation loop of the protein kinase domain of the Flt3 protein (UniProt.org). D839A has been demonstrated to occur as a secondary resistance mutation in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 25847190), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Jun 2018). Y
Y591D missense unknown FLT3 Y591D does not lie within any known functional domains of the Flt3 protein (UniProt.org). Y591D has been identified in sequencing studies (PMID: 14984498) but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Oct 2018).
D835N missense gain of function FLT3 D835N lies within the protein kinase domain activation loop of the Flt3 protein (UniProt.org, PMID: 11290608). D835N results in constitutive phosphorylation of Flt3 and activation of Stat5, Erk signaling, leading to transformation of cultured cells (PMID: 15256420).
F594L missense gain of function FLT3 F594L lies within the juxtamembrane domain of the Flt3 protein (PMID: 29164965). F594L results in constitutive phosphorylation of Flt3, activation of Stat5 signaling, and is transforming in culture (PMID: 16410449).
N676S missense unknown FLT3 N676S lies within the protein kinase domain of the Flt3 protein (UniProt.org). N676S has been demonstrated to occur as a secondary resistance mutation in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 25847190, PMID: 15374944), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Jun 2018). Y
L37S missense unknown FLT3 L37S lies within the extracellular domain of the Flt3 protein (UniProt.org). L37S has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
Y842H missense gain of function FLT3 Y842H lies within the protein kinase domain of the Flt3 protein (UniProt.org). Y842H results in increased phosphorylation of Flt3, activation of Stat5 and Mapk, and transformation of cultured cells (PMID: 14604974), and is associated with acquired resistance in the context of FLT3-ITD (PMID: 25847190, PMID: 22504184, PMID: 29187377). Y
D593_D600dup duplication gain of function - predicted FLT3 D593_D600dup indicates the insertion of 8 duplicate amino acids, aspartic acid (D)-593 through aspartic acid (D)-600, in the juxtamembrane domain of the Flt3 protein (PMID: 14759363). FLT3 D593_D600dup has not been biochemically characterized, but can be predicted to lead to activation of Flt3 based on the effects of other Flt3 internal tandem duplication (ITD) mutations (PMID: 12970773, PMID: 9737679, PMID: 11090077).
A627T missense unknown FLT3 A627T lies within the protein kinase domain of the Flt3 protein (UniProt.org). A627T has been identified as a drug resistance mutation (PMID: 15374944), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Jun 2018). Y
A914D missense unknown FLT3 A914D lies within the protein kinase domain of the Flt3 protein (UniProt.org). A914D has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Sep 2018).
P733Q missense unknown FLT3 P733Q lies within the protein kinase domain of the Flt3 protein (UniProt.org). P733Q has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
D358V missense unknown FLT3 D358V lies within the extracellular domain of the Flt3 protein (UniProt.org). D358V has been identified in sequencing studies (PMID: 21984973), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Sep 2018).
I836F missense unknown FLT3 I836F lies within the protein kinase domain of the Flt3 protein (UniProt.org). I836F has been identified in sequencing studies (PMID: 16371029), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
S127F missense unknown FLT3 S127F lies within the extracellular domain of the Flt3 protein (UniProt.org). S127F has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
I836H missense unknown FLT3 I836H lies within the protein kinase domain of the Flt3 protein (UniProt.org). I836H has been identified in sequencing studies (PMID: 16912228), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
N841K missense unknown FLT3 N841K lies within the activation loop of the protein kinase domain of the Flt3 protein (UniProt.org). N841K has been demonstrated to occur as a secondary resistance mutation in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 25847190, PMID: 25487917), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Jun 2018). Y
V825* nonsense unknown FLT3 V825* results in a premature truncation of the Flt3 protein at amino acid 825 of 993 within the protein kinase domain of the Flt3 protein (UniProt.org). V825* has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
V579A missense gain of function FLT3 V579A does not lie within any known functional domains of the Flt3 protein (UniProt.org). V579A results in constitutive phosphorylation of Flt3, activation of Stat5 signaling, and is transforming in culture (PMID: 16410449).
A848P missense unknown FLT3 A848P lies within the protein kinase domain of the Flt3 protein (UniProt.org). A848P has been identified in the scientific literature (PMID: 20520641), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
D835V missense gain of function FLT3 D835V lies within the protein kinase domain activation loop of the Flt3 protein (UniProt.org, PMID: 11290608). D835V results in constitutive phosphorylation of Flt3 and activation of Stat5, Erk signaling, leading to transformation of cultured cells (PMID: 15256420), and has been demonstrated to promote secondary drug resistance in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 22504184, PMID: 29187377). Y
Y599_D600insSTDNEYFYVDFREYEY insertion gain of function - predicted FLT3 Y599_D600insSTDNEYFYVDFREYEY results in the insertion of sixteen amino acids in the juxtamembrane domain of the Flt3 protein between amino acids 599 and 600 (UniProt.org). Y599_D600insSTDNEYFYVDFREYEY has not been biochemically characterized, but can be predicted to lead to activation of Flt3 based on the effects of other Flt3 internal tandem duplication (ITD) mutations (PMID: 12970773, PMID: 9737679, PMID: 11090077).
R845G missense unknown FLT3 R845G lies within the activation loop of the protein kinase domain of the Flt3 protein (UniProt.org). R845G has been demonstrated to occur as a secondary resistance mutation in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 25847190), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Jun 2018). Y
G831E missense unknown FLT3 G831E lies within the protein kinase domain of the Flt3 protein (UniProt.org). G831E demonstrates autophosphorylation and activation of downstream signaling at similar levels to wild-type Flt3 in culture, but is also predicted to stabilize the autoinhibitory conformation of the Flt3 protein and lead to a loss of function based on structural modeling (PMID: 18068628) and therefore, its effect on Flt3 protein function is unknown.
D839H missense unknown FLT3 D839H lies within the protein kinase domain of the Flt3 protein (UniProt.org). D839H has been demonstrated to occur as a secondary resistance mutation in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 19318574), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Jun 2018). Y
over exp none no effect FLT3 over exp indicates an over expression of the Flt3 protein and/or mRNA. However, the mechanism causing the over expression is unspecified.
D835A missense gain of function FLT3 D835A lies within the protein kinase domain activation loop of the Flt3 protein (UniProt.org, PMID: 11290608). D835A results in constitutive phosphorylation of Flt3 and activation of Stat5, Erk signaling, leading to transformation of cultured cells (PMID: 15256420).
S618L missense unknown FLT3 S618L lies within the protein kinase domain of the Flt3 protein (UniProt.org). S618L has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
Y599_D600insPAPQIMSTSTLISENMNIA insertion gain of function - predicted FLT3 Y599_D600insPAPQIMSTSTLISENMNIA results in the insertion of nineteen amino acids in the juxtamembrane domain of the Flt3 protein between amino acids 599 and 600 (UniProt.org). Y599_D600insPAPQIMSTSTLISENMNIA has not been biochemically characterized, but can be predicted to lead to activation of Flt3 based on the effects of other Flt3 internal tandem duplication (ITD) mutations (PMID: 12970773, PMID: 9737679, PMID: 11090077).
A680fs frameshift loss of function - predicted FLT3 A680fs results in a change in the amino acid sequence of the Flt3 protein beginning at aa 680 of 993, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the majority of the protein kinase domain (UniProt.org), A680fs is predicted to lead to a loss of Flt3 protein function.
K868N missense loss of function FLT3 K868N lies within the protein kinase domain of the Flt3 protein (UniProt.org). K868N inhibits Flt3 autophosphorylation and decreases Erk activity in cell culture (PMID: 27272783).
E964A missense unknown FLT3 E964A lies within the cytoplasmic domain of the Flt3 protein (UniProt.org). E964A has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
S585_F594dup duplication gain of function - predicted FLT3 S585_F594dup indicates the insertion of 10 duplicate amino acids, serine (S)-585 through phenylalanine (F)-594, in the juxtamembrane domain of the Flt3 protein (PMID: 14759363). S585_F594dup has not been biochemically characterized, but can be predicted to lead to activation of Flt3 based on the effects of other Flt3 internal tandem duplication (ITD) mutations (PMID: 12970773, PMID: 9737679, PMID: 11090077).
G846R missense unknown FLT3 G846R lies within the activation loop of the protein kinase domain of the Flt3 protein (UniProt.org). G846R has been demonstrated to occur as a secondary resistance mutation in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 25847190), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Jun 2018). Y
N609K missense unknown FLT3 N609K lies adjacent to the protein kinase domain of the Flt3 protein (UniProt.org). N609K has been identified in sequencing studies (PMID: 25847190), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
P532S missense unknown FLT3 P532S lies within the extracellular domain of the Flt3 protein (UniProt.org). P532S has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
Y572C missense gain of function FLT3 Y572C lies within the cytoplasmic domain of the Flt3 protein (UniProt.org). Y572C results in constitutive phosphorylation of Flt3, activation of Erk, Akt and Stat signaling, and is transforming in cell culture (PMID: 18068628).
F406C missense unknown FLT3 F406C lies within the extracellular domain of the Flt3 protein (UniProt.org). F406C has been identified in sequencing studies (PMID: 23856246), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
E366* nonsense loss of function - predicted FLT3 E366* results in a premature truncation of the Flt3 protein at amino acid 366 of 993 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), E366* is predicted to lead to a loss of Flt3 protein function.
wild-type none no effect Wild-type FLT3 indicates that no mutation has been detected within the FLT3 gene.
V579fs frameshift loss of function - predicted FLT3 V579fs results in a change in the amino acid sequence of the Flt3 protein beginning at aa 579 of 993, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), V579fs is predicted to lead to a loss of function.
T227M missense unknown FLT3 T227M lies within the extracellular domain of the Flt3 protein (UniProt.org). T227M has been identified in sequencing studies (PMID: 26999641, PMID: 29519565), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
Y599F missense loss of function FLT3 Y599F lies within the cytoplasmic domain of the Flt3 protein (UniProt.org). Y599F results in sustained ligand-dependent phosphorylation of Flt3, but decreased ligand-dependent Erk activation and cell survival in culture due to the loss of Shp2 interaction (PMID: 16684964).
P54L missense unknown FLT3 P54L lies within the extracellular domain of the Flt3 protein (UniProt.org). P54L has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Oct 2018).
E611fs frameshift loss of function - predicted FLT3 E611fs results in a change in the amino acid sequence of the Flt3 protein beginning at aa 611 of 993, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), E611fs is predicted to lead to a loss of function.
C695S missense unknown FLT3 C695S lies within the protein kinase domain of the Flt3 protein (UniProt.org). C695S has been demonstrated to confer resistance to FF-10101-01 (PMID: 29187377), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Oct 2018). Y
D835X missense gain of function - predicted FLT3 D835X indicates any Flt3 missense mutation that results in the aspartic acid (D) at amino acid 835 being replaced by a different amino acid. FLT3 codon 835 mutations are "hotspot" mutations that often results in constitutive phosphorylation of Flt3 and activation of downstream signaling (PMID: 11290608, PMID: 15256420) and therefore, are predicted to lead to a gain of Flt3 protein function.
N609fs frameshift loss of function - predicted FLT3 N609fs results in a change in the amino acid sequence of the Flt3 protein beginning at aa 609 of 993, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), N609fs is predicted to lead to a loss of function.
I38V missense unknown FLT3 I38V lies within the extracellular domain of the Flt3 protein (UniProt.org). I38V has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
I836_M837del deletion unknown FLT3 I836_M837del results in the deletion of two amino acids in the protein kinase domain of the Flt3 protein from amino acids 836 to 837 (UniProt.org). I836_M837del has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
E608fs frameshift loss of function - predicted FLT3 E608fs results in a change in the amino acid sequence of the Flt3 protein beginning at aa 608 of 993, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), E608fs is predicted to lead to a loss of function.
I836_M837insIRC insertion unknown FLT3 I836_M837insIRC results in the insertion of three amino acids in the protein kinase domain of the Flt3 protein between amino acids 836 and 837 (UniProt.org). I836_M837insIRC has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Oct 2018).
K290T missense unknown FLT3 K290T lies within the Ig-like C2-type domain of the Flt3 protein (UniProt.org). K290T has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
E366D missense unknown FLT3 E366D lies within the extracellular domain of the Flt3 protein (UniProt.org). E366D has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
D698N missense unknown FLT3 D698N lies within the protein kinase domain of the Flt3 protein (UniProt.org). D698N has been demonstrated to occur as a secondary resistance mutation in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 25847190), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Jun 2018). Y
V581* nonsense loss of function - predicted FLT3 V581* results in a premature truncation of the Flt3 protein at amino acid 581 of 993 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), V581* is predicted to lead to a loss of function.
N841Y missense unknown FLT3 N841Y lies within the activation loop of the protein kinase domain of the Flt3 protein (UniProt.org). N841Y has been identified in sequencing studies (PMID: 15625552), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
I836del deletion gain of function FLT3 I836del results in the deletion of an amino acid in the protein kinase domain activation loop of the Flt3 protein at amino acid 836 (PMID: 12663439). I836del results in constitutive phosphorylation of Flt3 and activation of Stat5, Erk signaling, leading to transformation of cultured cells (PMID: 15256420).
I417L missense unknown FLT3 I417L lies within the extracellular domain of the Flt3 protein (UniProt.org). I417L has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Oct 2018).
M837G missense unknown FLT3 M837G lies within the protein kinase domain of the Flt3 protein (UniProt.org). M837G has been demonstrated to confer drug resistance when in the context of FLT3 internal tandem duplication (FLT3-ITD) compound mutations co-occurring in tandem with S838R and D839H (PMID: 25847190), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Oct 2018). Y
M837P missense unknown FLT3 M837P lies within the protein kinase domain of the Flt3 protein (UniProt.org). M837P has been identified in sequencing studies (PMID: 16371029), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
V637I missense unknown FLT3 V637I lies within the protein kinase domain of the Flt3 protein (UniProt.org). V637I has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
V581fs frameshift loss of function - predicted FLT3 V581fs results in a change in the amino acid sequence of the Flt3 protein beginning at aa 581 of 993, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), V581fs is predicted to lead to a loss of function.
V824fs frameshift unknown FLT3 V824fs results in a change in the amino acid sequence of the Flt3 protein beginning at aa 824 of 993, likely resulting in premature truncation of the functional protein (UniProt.org). V824fs has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
I836X missense unknown FLT3 I836X indicates any Flt3 missense mutation which results in the isoleucine (I) at amino acid 836 being replaced by a different amino acid.
F590_F605dup duplication gain of function FLT3 F590_F605dup indicates the insertion of 16 duplicate amino acids, phenylalanine (F)-590 through phenylalanine (F)-605, in the juxtamembrane region of the Flt3 protein (PMID: 11756186). F590_F605dup results in constitutive phosphorylation of Flt3, activation of Stat5 and Erk signaling, and transformation of cells in culture (PMID: 10698507).
E236* nonsense loss of function - predicted FLT3 E236* results in a premature truncation of the Flt3 protein at amino acid 236 of 993 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), E236* is predicted to lead to a loss of Flt3 protein function.
N587fs frameshift loss of function - predicted FLT3 N587fs results in a change in the amino acid sequence of the Flt3 protein beginning at aa 587 of 993, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), N587fs is predicted to lead to a loss of function.
D835G missense gain of function - predicted FLT3 D835G lies within the activation loop of the protein kinase domain of the Flt3 protein (UniProt.org, PMID: 11290608). D835G results in autophosphorylation of Flt3 in one study (PMID: 28077790) and therefore, is predicted to lead to a gain of Flt3 protein function.
E880K missense unknown FLT3 E880K lies within the protein kinase domain of the Flt3 protein (UniProt.org). E880K has been identified in sequencing studies (PMID: 26343386), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
R595_L601dup duplication gain of function FLT3 R595_L601dup (also referred to as FLT3 L601_K602insREYEYDL) indicates the insertion of 7 duplicate amino acids, arginine (R)-595 through leucine(L)-601, in the juxtamembrane region of the Flt3 protein (PMID: 11756186). R595_L601dup results in constitutive phosphorylation of Flt3, activation of Stat5 and Erk signaling, transformation of cells in culture, and induction of myeloproliferative disorder in mouse models (PMID: 18068628, PMID: 11756186).
K826fs frameshift unknown FLT3 K826fs results in a change in the amino acid sequence of the Flt3 protein beginning at aa 826 of 993, likely resulting in premature truncation of the functional protein (UniProt.org). K826fs has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
S451E missense unknown FLT3 S451E lies within the extracellular domain of the Flt3 protein (UniProt.org). S451E has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Oct 2018).
E140* nonsense loss of function - predicted FLT3 E140* results in a premature truncation of the Flt3 protein at amino acid 140 of 993 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), E140* is predicted to lead to a loss of Flt3 protein function.
I867S missense gain of function FLT3 I867S lies within the protein kinase domain of the Flt3 protein (UniProt.org). I867S results in constitutive phosphorylation of Flt3 and activation of Akt signaling, leading to transformation of cultured cells (PMID: 24608088)
N676D missense unknown FLT3 N676D lies within the protein kinase domain of the Flt3 protein (UniProt.org). N676D has been demonstrated to occur as a secondary resistance mutation in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 22875611, PMID: 15374944), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Jun 2018). Y
E612_F613insGYVDFREYEYDLKWEFRPRENLEF insertion gain of function - predicted FLT3 E612_F613insGYVDFREYEYDLKWEFRPRENLEF results in the insertion of 24 amino acids in the cytoplasmic juxtamembrane region of the Flt3 protein between amino acids E612 and F613 (UniProt.org, PMID: 11756186). E612_F613insGYVDFREYEYDLKWEFRPRENLEF results in transformation of cultured cells (PMID: 11756186) and therefore, is predicted to lead to a gain of Flt3 protein function.
C184* nonsense loss of function - predicted FLT3 C184* results in a premature truncation of the Flt3 protein at amino acid 184 of 993 (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), C184* is predicted to lead to a loss of Flt3 protein function.
V843A missense unknown FLT3 V843A lies within the protein kinase domain of the Flt3 protein (UniProt.org). V843A has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
G697R missense unknown FLT3 G697R lies within the protein kinase domain of the Flt3 protein (UniProt.org). G697R has been demonstrated to occur as a secondary resistance mutation in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 15374944, PMID: 22875611), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Jun 2018). Y
E415K missense unknown FLT3 E415K lies within the extracellular domain of the Flt3 protein (UniProt.org). E415K has been identified in sequencing studies (PMID: 25303977), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
D750Y missense unknown FLT3 D750Y lies within the protein kinase domain of the Flt3 protein (UniProt.org). D750Y has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
T167A missense no effect - predicted FLT3 T167A lies within the extracellular domain of the Flt3 protein (UniProt.org). T167A does not result in IL-3 independent growth of cultured cells in one study (PMID: 18068628) and therefore, is predicted to have no effect on Flt3 protein function.
L610fs frameshift loss of function - predicted FLT3 L610fs results in a change in the amino acid sequence of the Flt3 protein beginning at aa 610 of 993, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), L610fs is predicted to lead to a loss of function.
L678M missense unknown FLT3 L678M lies within the protein kinase domain of the Flt3 protein (UniProt.org). L678M has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
P606L missense unknown FLT3 P606L lies within the cytoplasmic domain of the Flt3 protein (UniProt.org). P606L has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Oct 2018).
P888S missense unknown FLT3 P888S lies within the protein kinase domain of the Flt3 protein (UniProt.org). P888S has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
Y457C missense unknown FLT3 Y457C lies within the extracellular domain of the Flt3 protein (UniProt.org). Y457C has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
Y842S missense unknown FLT3 Y842S lies within the activation loop of the protein kinase domain of the Flt3 protein (UniProt.org). Y842S has been demonstrated to occur as a secondary resistance mutation in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 25847190), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Jun 2018). Y
D839G missense gain of function FLT3 D839G lies within the protein kinase domain activation loop of the Flt3 protein (UniProt.org). D839G results in constitutive phosphorylation of Flt3, activation of Akt and Mapk signaling, leading to transformation of cultured cells (PMID: 24608088), and has been demonstrated to occur as a secondary resistance mutation in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 25847190). Y
H821fs frameshift unknown FLT3 H821fs results in a change in the amino acid sequence of the Flt3 protein beginning at aa 821 of 993, likely resulting in premature truncation of the functional protein (UniProt.org). H821fs has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
S652G missense unknown FLT3 S652G lies within the protein kinase domain of the Flt3 protein (UniProt.org). S652G has been identified in sequencing studies (PMID: 25847190), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
G617E missense unknown FLT3 G617E lies within the protein kinase domain of the Flt3 protein (UniProt.org). G617E has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
P893L missense unknown FLT3 P893L lies within the protein kinase domain of the Flt3 protein (UniProt.org). P893L has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
R834Q missense gain of function FLT3 R834Q lies within the protein kinase domain of the Flt3 protein (UniProt.org). R834Q results in constitutive phosphorylation of Flt3, activation of Erk signaling, and is transforming in culture (PMID: 18068628).
R174K missense unknown FLT3 R174K lies within the extracellular domain of the Flt3 protein (UniProt.org). R174K has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
Y599_D600insGLYVDFREYEY insertion gain of function - predicted FLT3 Y599_D600insGLYVDFREYEY results in the insertion of 11 amino acids in the cytoplasmic juxtamembrane region of the Flt3 protein between amino acids 599 and 600 (PMID: 11756186). Y599_D600insGLYVDFREYEY results in transformation in cell culture (PMID: 11756186) and therefore, is predicted to lead to a gain of Flt3 protein function.
T628I missense unknown FLT3 T628I lies within the protein kinase domain of the Flt3 protein (UniProt.org). T628I has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
Y364H missense no effect - predicted FLT3 Y364H lies within the extracellular domain of the Flt3 protein (PMID: 18068628). Y364H does not result in IL-3 independent growth of cultured cells in one study (PMID: 18068628) and therefore, is predicted to have no effect on Flt3 protein function.
D895Y missense unknown FLT3 D895Y lies within the protein kinase domain of the Flt3 protein (UniProt.org). D895Y has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
G905V missense unknown FLT3 G905V lies within the protein kinase domain of the Flt3 protein (UniProt.org). G905V has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
R849fs frameshift unknown FLT3 R849fs results in a change in the amino acid sequence of the Flt3 protein beginning at aa 849 of 993, likely resulting in premature truncation of the functional protein (UniProt.org). R849fs has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
V220G missense unknown FLT3 V220G lies within the extracellular domain of the Flt3 protein (UniProt.org). V220G has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
act mut unknown gain of function FLT3 act mut indicates that this variant results in a gain of function in the FLT3 protein. However, the specific amino acid change has not been identified.
D324N missense unknown FLT3 D324N lies within the Ig-like C2-type domain of the Flt3 protein (UniProt.org). D324N has been identified in sequencing studies (PMID: 27534895), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Sep 2018).
D835E missense gain of function FLT3 D835E lies within the protein kinase domain activation loop of the Flt3 protein (UniProt.org, PMID: 11290608). D835E results in constitutive phosphorylation of Flt3 and activation of Stat5, Erk signaling, leading to transformation of cultured cells (PMID: 15256420).
F612fs frameshift loss of function - predicted FLT3 F612fs results in a change in the amino acid sequence of the Flt3 protein beginning at aa 612 of 993, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the protein kinase domain (UniProt.org), F612fs is predicted to lead to a loss of function.
R387Q missense unknown FLT3 R387Q lies within the extracellular domain of the Flt3 protein (UniProt.org). R387Q has been identified in sequencing studies (PMID: 26689913), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
rearrange unknown unknown FLT3 rearrangement indicates an unspecified rearrangement of the FLT3 gene.
E598_Y599insDVDFREYE insertion gain of function - predicted FLT3 E598_Y599insDVDFREYE results in the insertion of eight amino acids in the Flt3 protein between amino acids 598 and 599 (UniProt.org). E598_Y599insDVDFREYE has not been biochemically characterized, but can be predicted to lead to activation of Flt3 based on the effects of other Flt3 internal tandem duplication (ITD) mutations (PMID: 12970773, PMID: 9737679, PMID: 11090077).
L699F missense unknown FLT3 L699F lies within the protein kinase domain of the Flt3 protein (UniProt.org). L699F has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
L850fs frameshift unknown FLT3 L850fs results in a change in the amino acid sequence of the Flt3 protein beginning at aa 850 of 993, likely resulting in premature truncation of the functional protein (UniProt.org). L850fs has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
S454L missense unknown FLT3 S454L lies within the extracellular domain of the Flt3 protein (UniProt.org). S454L has been identified in sequencing studies (PMID: 25056374), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
F691I missense unknown FLT3 F691I lies within the protein kinase domain of the Flt3 protein (PMID: 23430109). F691I has been demonstrated to promote secondary drug resistance in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 23392356, PMID: 22409268), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Jun 2018). Y
G619V missense unknown FLT3 G619V lies within the protein kinase domain of the Flt3 protein (UniProt.org). G619V has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
V592A missense gain of function FLT3 V592A lies within the cytoplasmic domain of the Flt3 protein (UniProt.org). V592A results in constitutive phosphorylation of Flt3, activation of Stat5 signaling, upregulation of Bcl-x(L), and is transforming in cell culture (PMID: 16410449).
L576R missense gain of function FLT3 L576R does not lie within any known functional domains of the Flt3 protein (UniProt.org). L576R results in increased phosphorylation of Flt3 and Stat5 in culture (EHA, June 2017, abstr P184).
P986L missense unknown FLT3 P986L lies within the cytoplasmic domain of the Flt3 protein (UniProt.org). P986L has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
N847fs frameshift unknown FLT3 N847fs results in a change in the amino acid sequence of the Flt3 protein beginning at aa 847 of 993, likely resulting in premature truncation of the functional protein (UniProt.org). N847fs has not been characterized in the scientific literature and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2018).
N676K missense gain of function FLT3 N676K lies within the protein kinase domain of the Flt3 protein (UniProt.org). N676K results in constitutive phosphorylation of Flt3, activation of Akt and Mapk signaling, leading to malignant hematological transformation in animal models (PMID: 26891877), and has been demonstrated to occur as a resistance mutation in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 16150941). Y
Molecular Profile Protein Effect Treatment Approaches
FLT3 D835F unknown
FLT3 exon 14 ins FLT3 D835F
FLT3 F594_D600dup gain of function - predicted FLT3 Inhibitor
FLT3 V592G gain of function FLT3 Inhibitor
FLT3 Y597_K602dup gain of function - predicted FLT3 Inhibitor
FLT3 exon 14 ins FLT3 S652G
FLT3 exon 14 ins FLT3 F691I
FLT3 exon 14 ins FLT3 F691L FLT3 N841K
FLT3 exon 14 ins FLT3 M837G FLT3 S838R FLT3 D839H
FLT3 exon 14 ins FLT3 D835N
FLT3 exon 14 ins FLT3 F691L FLT3 D839N
FLT3 exon 14 ins FLT3 D839G
FLT3 exon 14 ins NPM1 mutant
FLT3 exon 14 ins FLT3 F691L FLT3 Y842C
FLT3 exon 14 ins FLT3 F691L
FLT3 exon 14 ins FLT3 F691L FLT3 D835Y
FLT3 exon 14 ins gain of function - predicted FLT3 Inhibitor
FLT3 ITD FLT3 Y842C
FLT3 exon 14 ins FLT3 N676D
FLT3 exon 14 ins FLT3 F691L FLT3 Y842S
FLT3 exon 14 ins FLT3 F691L FLT3 D835H
FLT3 exon 14 ins FLT3 F691L FLT3 R834Q
FLT3 exon 14 ins FLT3 D835E
FLT3 exon 14 ins FLT3 G846R
FLT3 exon 14 ins FLT3 D835G
FLT3 exon 14 ins FLT3 Y842S
FLT3 exon 14 ins FLT3 Y842H
FLT3 exon 14 ins FLT3 D839A
FLT3 exon 14 ins FLT3 D839H
FLT3 D835X FLT3 exon 14 ins
FLT3 exon 14 ins FLT3 D835Y
FLT3 exon 14 ins FLT3 D698N
FLT3 exon 14 ins FLT3 F691L FLT3 D839A
FLT3 exon 14 ins FLT3 T820A
FLT3 exon 14 ins FLT3 D835V
FLT3 exon 14 ins FLT3 F691L FLT3 D698N
FLT3 exon 14 ins FLT3 R834Q
FLT3 exon 14 ins FLT3 F691L FLT3 R845G
FLT3 exon 14 ins FLT3 D835H
FLT3 exon 14 ins FLT3 N676S
FLT3 exon 14 ins FLT3 D839N
FLT3 exon 14 ins FLT3 F691L FLT3 D839G
FLT3 exon 14 ins FLT3 Y842C
FLT3 exon 14 ins FLT3 F691L FLT3 Y842H
FLT3 exon 14 ins FLT3 F691L FLT3 G846R
FLT3 exon 14 ins FLT3 R845G
FLT3 exon 14 ins FLT3 F621L
FLT3 exon 14 ins FLT3 A848P
FLT3 exon 14 ins FLT3 F691L FLT3 D835N
FLT3 exon 14 ins FLT3 F691L FLT3 D835G
FLT3 exon 14 ins FLT3 M664I FLT3 F691L
FLT3 exon 14 ins FLT3 M664I
FLT3 exon 14 ins FLT3 N841K
FLT3 ITD FLT3 N676D FLT3 Y842C
FLT3 exon 14 ins FLT3 N676S FLT3 F691L
FLT3 exon 14 ins FLT3 F691L FLT3 D835E
FLT3 ITD FLT3 F691L
FLT3 V819I unknown
FLT3 W603_E604insDREYEYDLKW gain of function - predicted FLT3 Inhibitor
FLT3 mutant unknown
DNMT3A mut FLT3 mut NPM1 mut
FLT3 F691L unknown
FLT3 T136N unknown
FLT3 S838R unknown
FLT3 G822R unknown
FLT3 N841I gain of function FLT3 Inhibitor
FLT3 V194M no effect - predicted
FLT3 S840_N841insGS gain of function FLT3 Inhibitor
FLT3 F590_Y591delinsGD gain of function FLT3 Inhibitor
FLT3 Y599_D600insEYEYEYEY gain of function - predicted FLT3 Inhibitor
FLT3 F594Y gain of function FLT3 Inhibitor
FLT3 L611_E612insCSSDNEYFYVDFREYEYDLKWEFPRENL gain of function FLT3 Inhibitor
FLT3 S985fs unknown
FLT3 F621L unknown
FLT3 V557A unknown
FLT3 R607fs loss of function - predicted
FLT3 E77K unknown
FLT3 D835Y FLT3 N676D
FLT3 D835Y gain of function FLT3 Inhibitor
FLT3 E598_Y599insGLVQVTGSSDNEYFYVDFREYE gain of function FLT3 Inhibitor
FLT3 M664I unknown
FLT3 D7G unknown
FLT3 D835del gain of function FLT3 Inhibitor
FLT3 A450E unknown
FLT3 amp no effect FLT3 Inhibitor
FLT3 positive unknown
FLT3 R933L unknown
FLT3 F804C unknown
FLT3 K438fs loss of function - predicted
FLT3 V557I unknown
FLT3 A680V gain of function - predicted FLT3 Inhibitor
FLT3 D839A unknown
FLT3 L832F unknown
FLT3 F594C gain of function FLT3 Inhibitor
FLT3 P738R unknown
FLT3 Y842C gain of function FLT3 Inhibitor
FLT3 F590G unknown
FLT3 T820A unknown
FLT3 M737I no effect - predicted
FLT3 G282R unknown
FLT3 S451F gain of function FLT3 Inhibitor
FLT3 D835H gain of function FLT3 Inhibitor
FLT3 S71I unknown
FLT3 I836M unknown
FLT3 N676T unknown
FLT3 V197A unknown
FLT3 E708G unknown
FLT3 D870E unknown
FLT3 D839N unknown
FLT3 Y591D unknown
FLT3 D835N gain of function FLT3 Inhibitor
FLT3 F594L gain of function FLT3 Inhibitor
FLT3 N676S unknown
FLT3 L37S unknown
FLT3 Y842H gain of function FLT3 Inhibitor
FLT3 D593_D600dup gain of function - predicted FLT3 Inhibitor
FLT3 A627T unknown
FLT3 A914D unknown
FLT3 P733Q unknown
FLT3 D358V unknown
FLT3 I836F unknown
FLT3 S127F unknown
FLT3 I836H unknown
FLT3 N841K unknown
FLT3 V825* unknown
FLT3 V579A gain of function FLT3 Inhibitor
FLT3 A848P unknown
FLT3 D835V gain of function FLT3 Inhibitor
DNMT3A R882H FLT3 Y599_D600insSTDNEYFYVDFREYEY NPM1 W288fs
FLT3 Y599_D600insSTDNEYFYVDFREYEY gain of function - predicted FLT3 Inhibitor
IDH2 R140W FLT3 Y599_D600insSTDNEYFYVDFREYEY
FLT3 R845G unknown
FLT3 G831E unknown
FLT3 D839H unknown
FLT3 over exp no effect FLT3 Inhibitor
FLT3 D835A gain of function FLT3 Inhibitor
FLT3 S618L unknown
FLT3 Y599_D600insPAPQIMSTSTLISENMNIA gain of function - predicted FLT3 Inhibitor
FLT3 A680fs loss of function - predicted
FLT3 K868N loss of function
FLT3 E964A unknown
FLT3 S585_F594dup gain of function - predicted FLT3 Inhibitor
FLT3 G846R unknown
FLT3 N609K unknown
FLT3 P532S unknown
FLT3 Y572C gain of function FLT3 Inhibitor
FLT3 F406C unknown
FLT3 E366* loss of function - predicted
FLT3 wild-type no effect
NPM1 mutant FLT3 wild-type
FLT3 V579fs loss of function - predicted
FLT3 T227M unknown
FLT3 Y599F loss of function
FLT3 P54L unknown
FLT3 E611fs loss of function - predicted
FLT3 C695S unknown
FLT3 D835X gain of function - predicted FLT3 Inhibitor
FLT3 N609fs loss of function - predicted
FLT3 I38V unknown
FLT3 I836_M837del unknown
FLT3 E608fs loss of function - predicted
FLT3 I836_M837insIRC unknown
FLT3 K290T unknown
FLT3 E366D unknown
FLT3 D698N unknown
FLT3 V581* loss of function - predicted
FLT3 N841Y unknown
FLT3 I836del gain of function FLT3 Inhibitor
FLT3 I417L unknown
FLT3 M837G unknown
FLT3 M837P unknown
FLT3 V637I unknown
FLT3 V581fs loss of function - predicted
FLT3 V824fs unknown
FLT3 I836X unknown
FLT3 F590_F605dup gain of function FLT3 Inhibitor
FLT3 E236* loss of function - predicted
FLT3 N587fs loss of function - predicted
FLT3 D835G gain of function - predicted FLT3 Inhibitor
FLT3 E880K unknown
FLT3 R595_L601dup gain of function FLT3 Inhibitor
FLT3 K826fs unknown
FLT3 S451E unknown
FLT3 E140* loss of function - predicted
FLT3 I867S gain of function FLT3 Inhibitor
FLT3 N676D unknown
FLT3 E612_F613insGYVDFREYEYDLKWEFRPRENLEF gain of function - predicted FLT3 Inhibitor
FLT3 C184* loss of function - predicted
FLT3 V843A unknown
FLT3 G697R unknown
FLT3 E415K unknown
FLT3 D750Y unknown
FLT3 T167A no effect - predicted
FLT3 L610fs loss of function - predicted
FLT3 L678M unknown
FLT3 P606L unknown
FLT3 P888S unknown
FLT3 Y457C unknown
FLT3 Y842S unknown
FLT3 D839G gain of function FLT3 Inhibitor
FLT3 H821fs unknown
FLT3 S652G unknown
FLT3 G617E unknown
FLT3 P893L unknown
FLT3 R834Q gain of function FLT3 Inhibitor
FLT3 R174K unknown
FLT3 Y599_D600insGLYVDFREYEY gain of function - predicted FLT3 Inhibitor
FLT3 T628I unknown
FLT3 Y364H no effect - predicted
FLT3 D895Y unknown
FLT3 G905V unknown
FLT3 R849fs unknown
FLT3 V220G unknown
FLT3 act mut gain of function FLT3 Inhibitor
FLT3 D324N unknown
FLT3 D835E gain of function FLT3 Inhibitor
FLT3 F612fs loss of function - predicted
FLT3 R387Q unknown
FLT3 rearrange unknown
FLT3 E598_Y599insDVDFREYE gain of function - predicted FLT3 Inhibitor
FLT3 L699F unknown
FLT3 L850fs unknown
FLT3 S454L unknown
FLT3 F691I unknown
FLT3 G619V unknown
FLT3 V592A gain of function FLT3 Inhibitor
FLT3 L576R gain of function FLT3 Inhibitor
FLT3 P986L unknown
FLT3 N847fs unknown
FLT3 N676K gain of function FLT3 Inhibitor
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 exon 14 ins FLT3 D835F acute myeloid leukemia predicted - sensitive Crenolanib Preclinical - Patient cell culture Actionable In a preclinical study, Crenolanib inhibited growth of blasts derived from a patient with acute myeloid leukemia harboring FLT3 internal tandem duplication (ITD) and FLT3 D835F (PMID: 24227820). 24227820
FLT3 exon 14 ins FLT3 D835F acute myeloid leukemia predicted - resistant Sorafenib Clinical Study Actionable In a clinical case study, FLT3 D835F was identified as an acquired mutation in a patient with acute myeloid leukemia harboring FLT3 internal tandem duplication (ITD) whose disease progressed on Nexavar (sorafenib) after initial response (PMID: 24227820). 24227820
FLT3 exon 14 ins FLT3 D835F Advanced Solid Tumor sensitive MRX-2843 Preclinical - Cell culture Actionable In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing both FLT3 internal tandem duplication (ITD) and D835F in culture (PMID: 27158668). 27158668
FLT3 exon 14 ins FLT3 D835F Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D835F were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 V592G Advanced Solid Tumor sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited FLT3-induced phosphorylation of ERK1/2 and reduced growth of transformed cells expressing FLT3 V592G in culture (PMID: 18068628). 18068628
FLT3 exon 14 ins FLT3 S652G leukemia resistant Pexidartinib Clinical Study Actionable In a clinical study, a patient with FLT3-ITD positive leukemia initially responded to PLX3397, but experienced relapse after emergence of a FLT3 S652G mutation on the same allele as FLT3-ITD (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691I Advanced Solid Tumor decreased response Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and F691I demonstrated reduced response to Sutent (sunitinib) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 F691I Advanced Solid Tumor resistant Sorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and F691I were resistant to Nexavar (sorafenib) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 F691I Advanced Solid Tumor resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and F691I were resistant to Rydapt (midostaurin) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 F691I Advanced Solid Tumor resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and F691I were resistant to Quizartinib (AC220) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 F691I Advanced Solid Tumor decreased response Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3 ITD and F691I demonstrated reduced sensitivity to Alunbrig (brigatinib) compared to cells expressing FLT3 ITD in culture (PMID: 27780853). 27780853
FLT3 exon 14 ins FLT3 F691L FLT3 N841K Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/N841K mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 M837G FLT3 S838R FLT3 D839H leukemia resistant Pexidartinib Clinical Study Actionable In a clinical study, a leukemia patient with FLT3-ITD positive leukemia initially responded to PLX3397, but experienced relapse after emergence of a compound FLT3 M837G/S838R/D839H mutation on the FLT3-ITD allele (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D835N Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D835N were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L FLT3 D839N Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/D839N were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D839G Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, FLT3 D835G conferred resistance to PLX3397 when expressed in a compound mutation with FLT3-ITD in cell culture (PMID: 25847190). 25847190
FLT3 exon 14 ins NPM1 mutant leukemia predicted - sensitive EPZ004777 Preclinical Actionable In a preclinical study, EPZ004777 inhibited growth and induced differentiation of murine leukemia cells expressing an NPM1 mutation and FLT3 internal tandem duplication in culture, and improved survival in mouse models (PMID: 27535106). 27535106
FLT3 exon 14 ins NPM1 mutant leukemia predicted - sensitive MI-503 Preclinical Actionable In a preclinical study, MI-503 inhibited growth of murine leukemia cells expressing an NPM1 mutation and FLT3 internal tandem duplication in culture, and improved survival in mouse models (PMID: 27535106). 27535106
FLT3 exon 14 ins NPM1 mutant acute myeloid leukemia sensitive ENMD-2076 Phase I Actionable In a Phase I trial, two acute myeloid leukemia patients co-harboring a FLT3-ITD mutation and NPM1 mutation demonstrated anti-leukemia activity when treated with ENMD-2076 (PMID: 27406088). 27406088
FLT3 exon 14 ins FLT3 F691L FLT3 Y842C Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/Y842C mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L Advanced Solid Tumor resistant Sorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and F691L were resistant to Nexavar (sorafenib) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 F691L Advanced Solid Tumor resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and F691L were resistant to Quizartinib (AC220) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 F691L acute myeloid leukemia sensitive FF-10101 Preclinical - Cell line xenograft Actionable In a preclinical study, FF-10101 inhibited Flt3 autophosphorylation and growth of leukemic cell lines and inhibited growth of cell line xenografts with FLT3-ITD/F691L compound mutations (PMID: 29187377). 29187377
FLT3 exon 14 ins FLT3 F691L leukemia sensitive Pexidartinib Preclinical Actionable In a preclinical study, PLX3397 inhibited proliferation of human leukemia cells harboring both FLT3-ITD and FLT3 F691L in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L leukemia sensitive E6201 Preclinical Actionable In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines harboring FLT3 F691L in addition to FLT3 internal tandem duplications (ITD) in culture (PMID: 26822154). 26822154
FLT3 exon 14 ins FLT3 F691L acute myeloid leukemia sensitive MRX-2843 Preclinical - Cell line xenograft Actionable In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant acute myeloid leukemia cells harboring FLT3 internal tandem duplication (ITD) and F691L in culture, and prolonged survival in cell line xenograft models (PMID: 27158668). 27158668
FLT3 exon 14 ins FLT3 F691L Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing FLT3 ITD and F691L in culture (PMID: 27780853). 27780853
FLT3 exon 14 ins FLT3 F691L Advanced Solid Tumor sensitive MRX-2843 Preclinical - Cell culture Actionable In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing both FLT3 internal tandem duplication (ITD) and F691L in culture (PMID: 27158668). 27158668
FLT3 exon 14 ins FLT3 F691L hematologic cancer sensitive G-749 Preclinical - Cell culture Actionable In a preclinical study, cells co-expressing a FLT3 internal tandem duplication and FLT3 F691L were sensitive to G-749 in culture, demonstrating inhibition of cell growth and inhibition of Flt3 autophosphorylation (PMID: 22864397). 22864397
FLT3 exon 14 ins FLT3 F691L acute myeloid leukemia decreased response Lestaurtinib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 F691L demonstrated a decreased response to Lestaurtinib (CEP-701) compared to treated cells harboring a FLT3 ITD and expressing FLT3 Y842C (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 F691L Advanced Solid Tumor sensitive Pexidartinib Preclinical Actionable In a preclinical study, PLX3397 inhibited growth of transformed cells expressing a compound FLT3 F691L/FLT3-ITD mutation in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L acute myeloid leukemia decreased response Midostaurin Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 F691L demonstrated a decreased response to Lestaurtinib (CEP-701) compared to treated cells harboring a FLT3 ITD and expressing FLT3 Y842C (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 F691L FLT3 D835Y Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/D835Y mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins acute myeloid leukemia sensitive Selinexor + Sorafenib Phase Ib/II Actionable In a Phase I/II trial, combination of Selinexor and Nexavar (sorafenib) treatment resulted in complete remission in 29% (4/14) and more than 50% blast reduction in 14% (2/14) of patients with acute myeloid leukemia harboring FLT3 ITD and/or D835 mutations (ASH, 59th Annual Meeting and Exposition, Dec 2017, Abstract 1344; NCT01607892). detail...
FLT3 exon 14 ins acute myeloid leukemia sensitive Cytarabine + G-749 Preclinical - Cell culture Actionable In a preclinical study, the combination of G-749 and Cytosar-U (cytarabine) resulted in a synergistic effect, demonstrating greater inhibition of proliferation compared to G-749 alone in acute myeloid leukemia cells harboring a FLT3 internal tandem duplication (PMID: 24532805). 24532805
FLT3 exon 14 ins acute myeloid leukemia sensitive Altiratinib Preclinical - Cell culture Actionable In a preclinical study, Altiratinib (DCC-0701) inhibited proliferation of an acute myeloid leukemia cell harboring a FLT3-ITD mutation in culture (PMID: 26285778). 26285778
FLT3 exon 14 ins acute myeloid leukemia sensitive FF-10101 Preclinical - Pdx & cell culture Actionable In a preclinical study, FF-10101 inhibited Flt3 autophosphorylation and cell growth of leukemic cells in culture and in AML-patient-derived xenograft models with FLT3-ITD mutations (PMID: 29187377). 29187377
FLT3 exon 14 ins leukemia predicted - sensitive GMI-1359 + Sorafenib Preclinical - Cell culture Actionable In a preclinical study, combination of GMI-1359 with Nexavar (sorafenib) enhanced apoptosis compared to Nexavar (sorafenib) alone (48.9% vs 36.6%) in leukemia cell lines harboring FLT3 internal tandem duplication (ITD) mutations (Blood 2015 126(23):3790). detail...
FLT3 exon 14 ins acute myeloid leukemia sensitive G-749 Preclinical - Cell line xenograft Actionable In a preclinical study, G-749 induced apoptosis in acute myeloid leukemia cells harboring a FLT3 internal tandem duplication in culture, and inhibited tumor growth and induced tumor regression in cell line xenograft models (PMID: 24532805). 24532805
FLT3 exon 14 ins Advanced Solid Tumor predicted - sensitive Cabozantinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing a FLT3-ITD mutation were sensitive to Cometriq (cabozantinib) in culture (PMID: 21926191). 21926191
FLT3 exon 14 ins acute myeloid leukemia sensitive Cytarabine + Daunorubicin + Midostaurin Phase III Actionable In a Phase III trial that supported FDA approval, treatment with Rydapt (midostaurin), combined with Cytosar-U (cytarabine) and Daunorubicin, improved overall survival (74.7 mo vs 25.6 mo) in patients with FLT3-mutant or FLT3-ITD acute myeloid leukemia compared to Cytosar-U (cytarabine) and Daunorubicin with placebo (PMID: 28644114). 28644114
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive Cytarabine + Daunorubicin + Quizartinib Phase I Actionable In a Phase I trial (QuANTUM-First), the combination therapy, Quizartinib (AC220) with Cytosar-U (cytarabine) and Cerubidine (daunorubicin), resulted in 67% (6/9) of acute myeloid leukemia patients harboring a FLT3-ITD achieving a composite complete response and two patients achieving morphologic leukemia-free state (PMID: 29139135; NCT01390337). 29139135
FLT3 exon 14 ins acute myeloid leukemia sensitive Ponatinib Preclinical - Patient cell culture Actionable In a preclinical study, Iclusig (ponatinib) inhibited viability of patient derived acute myeloid leukemia cells harboring FLT3 ITD mutations in culture, and inhibited growth of tumors in cell line xenograft models (PMID: 21482694). 21482694
FLT3 exon 14 ins acute myeloid leukemia sensitive Ponatinib Phase I Actionable In a Phase I trial, Iclusig (ponatinib) resulted in a 25% (3/12) overall response rate, indicated as partial remission or better, in acute myeloid leukemia patients harboring FLT3-ITD (PMID: 23691988). 23691988
FLT3 exon 14 ins acute myeloid leukemia sensitive Ki23819 Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication were sensitive to Ki23819 in culture, demonstrating inhibition of autophosphorylation and downstream signaling, and reduced cell proliferation (PMID: 15815726). 15815726
FLT3 exon 14 ins leukemia predicted - sensitive GMI-1359 Preclinical - Cell line xenograft Actionable In a preclinical study, GMI-1359 in combination with chemotherapy resulted in significant survival benefit compared to chemotherapy alone (67% vs 30%) in cell line xenograft models of FLT3-ITD leukemia (Blood 2015 126(23):3790). detail...
FLT3 exon 14 ins acute myeloid leukemia sensitive Quizartinib Phase I Actionable In a Phase I trial, acute myeloid leukemia (AML) pediatric patients harboring a FLT3-ITD mutation demonstrated a greater sensitivity to treatment with Quizartinib (AC220) when compared to AML patients with wild-type FLT3, resulting in three complete responses, four with stable disease, and a lower bone marrow blast cell count (PMID: 26920889). 26920889
FLT3 exon 14 ins acute myeloid leukemia no benefit rebastinib Phase I Actionable In a Phase I trial, acute myeloid leukemia patients harboring a FLT3 internal tandem duplication did not benefit from treatment with Rebastinib (DCC-2036) (PMID: 27927766). 27927766
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive SHP099 Preclinical - Pdx Actionable In a preclinical study, treatment with SHP099 resulted in reduction of CD45-positive leukemic cells and decreased splenomegaly in a human primary tumor-derived xenograft model of acute myeloid leukemia harboring a FLT3-ITD mutation (PMID: 27362227). 27362227
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive Azacitidine + Quizartinib Phase Ib/II Actionable In a Phase I/II trial, Quizartinib (AC220) in combination with Vidaza (azacitidine) resulted in a median overall survival of 13.4 months and a median progression-free survival of 6.9 months in acute myeloid leukemia patients harboring FLT3 ITD mutations (ASH 59th Annual Meeting and Exposition, Dec 2017, Abstract 723). detail...
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive Pacritinib Preclinical - Cell line xenograft Actionable In a preclinical study, Pacritinib (SB1518) induced apoptosis and inhibited proliferation of acute myeloid leukemia cells harboring a FLT3-ITD mutation in culture, and inhibited tumor growth and induced tumor regression in cell line xenograft models (PMID: 22829080). 22829080
FLT3 exon 14 ins acute myeloid leukemia sensitive MRX-2843 Preclinical - Cell line xenograft Actionable In a preclinical study, MRX-2843 inhibited Flt3 activation, resulted in growth inhibition in acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) in culture and in cell line xenograft models, and prolonged survival in patient-derived xenograft models (PMID: 27158668). 27158668
FLT3 exon 14 ins Advanced Solid Tumor sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) demonstrated efficacy in inhibiting proliferation and viability of transformed cells expressing a FLT3-ITD mutation in culture (PMID: 12124173). 12124173
FLT3 exon 14 ins acute myeloid leukemia sensitive ENMD-2076 Phase I Actionable In a Phase I trial, an acute myeloid leukemia patient with a FLT3-ITD mutation demonstrated anti-leukemia activity when treated with ENMD-2076 (PMID: 27406088). 27406088
FLT3 exon 14 ins acute myeloid leukemia sensitive E6201 Preclinical - Cell culture Actionable In a preclinical study, E6201 induced apoptosis in blast samples derived from acute myeloid leukemia patients harboring FLT3 internal tandem duplications (ITD) in culture (PMID: 26822154). 26822154
FLT3 exon 14 ins Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing FLT3 ITD in culture (PMID: 27780853). 27780853
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive Azacitidine + Sorafenib Guideline Actionable Nexavar (sorafenib) in combination with Vidaza (azacitidine) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org). detail...
FLT3 exon 14 ins acute myeloid leukemia sensitive Crenolanib Phase I Actionable In a Phase I trial, Crenolanib treatment resulted in an overall survival (OS) of 238 days in AML patients harboring FLT3 exon 14 insertions (ITD) that received no prior therapy, and an OS of 158 days in those progressed on TKIs (J Clin Oncol 34, 2016 (suppl; abstr 7008)). detail...
FLT3 exon 14 ins acute myeloid leukemia sensitive CG'806 Preclinical - Cell culture Actionable In a preclinical study, CG'806 inhibited Flt3 downstream signaling, induced G1 cell cycle arrest and apoptosis in acute myeloid leukemia cells harboring FLT3 ITD mutations in culture (Blood 2017 130:4629). detail...
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive Cytarabine + Quizartinib Phase Ib/II Actionable In a Phase I/II trial, Quizartinib (AC220) in combination with Cytosar-U (cytarabine) resulted in a median overall survival of 6.7 months and a median progression-free survival of 3 months in acute myeloid leukemia patients harboring FLT3 ITD mutations (ASH 59th Annual Meeting and Exposition, Dec 2017, Abstract 723). detail...
FLT3 exon 14 ins Advanced Solid Tumor sensitive Pexidartinib Preclinical Actionable In a preclinical study, PLX3397 inhibited proliferation of transformed cells expressing FLT3-ITD in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins acute myeloid leukemia not applicable N/A Guideline Prognostic FLT3 internal tandem duplication (FLT3-ITD) mutations are associated with inferior prognosis in acute myeloid leukemia patients with normal karyotype (NCCN.org). detail...
FLT3 exon 14 ins hematologic cancer sensitive GTP-14564 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing a FLT3 internal tandem duplication were sensitive to GTP-14564 treatment in culture, demonstrating decreased Stat5 activity and growth inhibition (PMID: 12815052). 12815052
FLT3 exon 14 ins leukemia sensitive E6201 Preclinical - Cell line xenograft Actionable In a preclinical study, E6201 induced growth inhibition and apoptosis in leukemia cell lines harboring FLT3 internal tandem duplications (ITD) and reduced tumor burden in xenograft models (PMID: 26822154). 26822154
FLT3 exon 14 ins acute myeloid leukemia sensitive GTP-14564 Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication were sensitive to GTP-14564 treatment in culture, demonstrating growth inhibition (PMID: 12815052). 12815052
FLT3 exon 14 ins leukemia sensitive Pexidartinib Preclinical - Cell line xenograft Actionable In a preclinical study, PLX3397 inhibited proliferation of human leukemia cells harboring FLT3-ITD in culture and in cell line xenograft models (PMID: 25847190). 25847190
FLT3 exon 14 ins acute myeloid leukemia sensitive Semaxanib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication were sensitive to Semaxanib (SU5416) in culture, demonstrating inhibition of cell proliferation and inhibition of Flt3, Mapk, and Stat5 phosphorylation (PMID: 12351406). 12351406
FLT3 exon 14 ins acute myeloid leukemia sensitive Gilteritinib Phase Ib/II Actionable In a Phase I/II trial, treatment with Gilteritinib (ASP2215) at a dose of 80mg/day or higher resulted in an overall response rate of 55% (77/141) in patients with relapsed or refractory acute myeloid leukemia harboring FLT3 internal tandem duplication mutations (PMID: 28645776; NCT02014558). 28645776
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive Decitabine + Sorafenib Guideline Actionable Nexavar (sorafenib) in combination with Dacogen (decitabine) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (FLT3-ITD) mutation (NCCN.org). detail...
FLT3 exon 14 ins leukemia sensitive FN-1501 Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with FN-1501 reduced phoshorylation of FLT3 and downstream STAT5, ERK, and AKT, induced apoptosis and cell-cycle arrest, and decreased proliferation in a human leukemia cell line harboring a FLT3-ITD mutation in culture, and induced tumor regression in xenograft models (PMID: 29357250). 29357250
FLT3 exon 14 ins FLT3 N676D Advanced Solid Tumor decreased response Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and N676D demonstrated reduced sensitivity to Quizartinib (AC220) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 N676D hematologic cancer sensitive G-749 Preclinical - Cell culture Actionable In a preclinical study, cells co-expressing a FLT3 internal tandem duplication and FLT3 N676D were sensitive to G-749 in culture, demonstrating inhibition of cell growth and inhibition of Flt3 autophosphorylation (PMID: 22864397). 22864397
FLT3 exon 14 ins FLT3 N676D Advanced Solid Tumor resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and N676D were resistant to Rydapt (midostaurin) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 F691L FLT3 Y842S Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/Y842S mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L FLT3 D835H Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/D835H mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L FLT3 R834Q Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691Q/R834Q mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D835E Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D835E were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 G846R Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 G846R were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D835G Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D835G were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 Y842S Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 Y842S were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 Y842H Advanced Solid Tumor decreased response Sorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and Y842H demonstrated reduced sensitivity to Nexavar (sorafenib) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 Y842H hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101, as compared to Quizartinib, inhibited Flt3 autophosphorylation and cell proliferation of transformed 32Dcl3 murine myeloid cells expressing a human FLT3-ITD/Y842H compound mutation (PMID: 29187377). 29187377
FLT3 exon 14 ins FLT3 Y842H Advanced Solid Tumor sensitive MRX-2843 Preclinical - Cell culture Actionable In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing both FLT3 internal tandem duplication (ITD) and Y842H in culture (PMID: 27158668). 27158668
FLT3 exon 14 ins FLT3 Y842H Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 Y842H were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 Y842H Advanced Solid Tumor decreased response Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and Y842H demonstrated reduced sensitivity to Quizartinib (AC220) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 D839A Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D839A were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D839H Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D839H were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 D835X FLT3 exon 14 ins acute myeloid leukemia sensitive Selinexor + Sorafenib Phase Ib/II Actionable In a Phase I/II trial, combination of Selinexor and Nexavar (sorafenib) treatment resulted in complete remission in 29% (4/14) and more than 50% blast reduction in 14% (2/14) of patients with acute myeloid leukemia harboring FLT3 ITD and/or D835 mutations (ASH, 59th Annual Meeting and Exposition, Dec 2017, Abstract 1344; NCT01607892). detail...
FLT3 D835X FLT3 exon 14 ins acute myeloid leukemia sensitive Crenolanib Phase I Actionable In a Phase I trial, Crenolanib treatment resulted in an overall survival (OS) of 128 days in AML patients harboring both FLT3 D835X and exon 14 insertion (ITD) that received no prior therapy, and an OS of 63 days in those progressed on TKIs (J Clin Oncol 34, 2016 (suppl; abstr 7008)). detail...
FLT3 exon 14 ins FLT3 D835Y Advanced Solid Tumor sensitive MRX-2843 Preclinical - Cell culture Actionable In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing both FLT3 internal tandem duplication (ITD) and D835Y in culture (PMID: 27158668). 27158668
FLT3 exon 14 ins FLT3 D835Y Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing FLT3 ITD and D835Y in culture (PMID: 27780853). 27780853
FLT3 exon 14 ins FLT3 D835Y Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, FLT3 D835Y conferred resistance to PLX3397 when expressed in a compound mutation with FLT3-ITD in cell culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D835Y leukemia resistant Pexidartinib Clinical Study Actionable In a clinical study, a patient with FLT3-ITD positive leukemia initially responded to PLX3397 therapy, but experienced relapse after emergence of FLT3 D835Y on the same allele as the FLT3-ITD mutation (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia sensitive FF-10101 Preclinical - Cell line xenograft Actionable In a preclinical study, FF-10101 inhibited Flt3 autophosphorylation and growth of leukemic cell lines and inhibited growth of cell line xenografts with FLT3-ITD/D835Y compound mutations (PMID: 29187377). 29187377
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia sensitive MRX-2843 Preclinical - Cell line xenograft Actionable In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant acute myeloid leukemia cells harboring FLT3 internal tandem duplication (ITD) and D835Y in culture, and prolonged survival in cell line xenograft models (PMID: 27158668). 27158668
FLT3 exon 14 ins FLT3 D698N Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D698N were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L FLT3 D839A Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/D835A mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D835V Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D835V were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D835V Advanced Solid Tumor sensitive MRX-2843 Preclinical - Cell culture Actionable In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing both FLT3 internal tandem duplication (ITD) and D835V in culture (PMID: 27158668). 27158668
FLT3 exon 14 ins FLT3 F691L FLT3 D698N Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/D698N mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 R834Q Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 R834Q were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L FLT3 R845G Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/R845G mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D835H acute myeloid leukemia sensitive FF-10101 Preclinical - Pdx Actionable In a preclinical study, FF-10101 inhibited cell growth in AML-patient-derived xenograft models with FLT3-ITD/D835H compound mutations (PMID: 29187377). 29187377
FLT3 exon 14 ins FLT3 D835H Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, FLT3 D835H conferred resistance to PLX3397 in transformed cells when expressed as a compound mutation with FLT3-ITD in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D835H leukemia resistant Pexidartinib Clinical Study Actionable In a clinical study, a patient with FLT3-ITD positive leukemia initially responded to PLX3397, but experienced relapse after emergence of a FLT3 D835H mutation on the same allele as the FLT3-ITD mutation (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 N676S Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 N676S were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D839N Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D839N were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L FLT3 D839G Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD /F691L/D839G mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 Y842C acute myeloid leukemia resistant Sorafenib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 Y842C demonstrated resistance to Nexavar (sorafenib) in culture (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 Y842C hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101, as compared to Quizartinib, inhibited Flt3 autophosphorylation and cell proliferation of transformed 32Dcl3 murine myeloid cells expressing a human FLT3-ITD/Y842C compound mutation (PMID: 29187377). 29187377
FLT3 exon 14 ins FLT3 Y842C acute myeloid leukemia resistant Sunitinib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 Y842C demonstrated resistance to Sutent (sunitinib) in culture (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 Y842C acute myeloid leukemia sensitive Lestaurtinib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 Y842C demonstrated sensitivity to Lestaurtinib (CEP-701) in culture (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 Y842C acute myeloid leukemia sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 Y842C demonstrated sensitivity to Rydapt (midostaurin) in culture (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 Y842C Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, FLT3 Y842C conferred resistance to PLX3397 when expressed in a compound mutation with FLT3-ITD in cell culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 Y842C Advanced Solid Tumor sensitive MRX-2843 Preclinical - Cell culture Actionable In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing both FLT3 internal tandem duplication (ITD) and Y842C in culture (PMID: 27158668). 27158668
FLT3 exon 14 ins FLT3 Y842C leukemia sensitive E6201 Preclinical Actionable In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines harboring FLT3 Y842C in addition to FLT3 internal tandem duplications (ITD) in culture (PMID: 26822154). 26822154
FLT3 exon 14 ins FLT3 Y842C acute myeloid leukemia resistant AGL2043 Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 Y842C demonstrated resistance to AGL2043 in culture (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 F691L FLT3 Y842H Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/Y842H mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L FLT3 G846R Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691Q/G846R mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 R845G Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 R845G were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F621L acute myeloid leukemia decreased response Sunitinib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication (ITD) and expressing FLT3 F621L demonstrated a decreased response to Sutent (sunitinib) in culture when compared to treated cells harboring a FLT3 ITD and expressing FLT3 Y842C (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 F621L acute myeloid leukemia sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication (ITD) and expressing FLT3 F621L demonstrated sensitivity to Rydapt (midostaurin) in culture (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 F621L acute myeloid leukemia sensitive Lestaurtinib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication (ITD) and expressing FLT3 F621L demonstrated sensitivity to Lestaurtinib (CEP-701) in culture (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 F621L acute myeloid leukemia sensitive Sorafenib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication (ITD) and expressing FLT3 F621L demonstrated sensitivity to Nexavar (sorafenib) in culture (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 F621L acute myeloid leukemia decreased response AGL2043 Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication (ITD) and expressing FLT3 F621L demonstrated a decreased response to AGL2043 in culture when compared to treated cells harboring a FLT3 ITD and expressing FLT3 Y842C (Blood 2009 114:3776). detail...
FLT3 exon 14 ins FLT3 A848P Advanced Solid Tumor decreased response Sorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and A848P demonstrated reduced sensitivity to Nexavar (sorafenib) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 A848P Advanced Solid Tumor decreased response Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and A848P demonstrated reduced sensitivity to Quizartinib (AC220) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 A848P Advanced Solid Tumor resistant Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and A848P were resistant to Sutent (sunitinib) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 F691L FLT3 D835N Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/D835N mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L FLT3 D835G Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/D835G mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 M664I FLT3 F691L Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/M664I mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 M664I Advanced Solid Tumor decreased response Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 M664I displayed reduced sensitivity to PLX3397 relative to cells expressing FLT3-ITD in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 N841K Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 N841K were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 ITD FLT3 N676D FLT3 Y842C leukemia sensitive E6201 Preclinical Actionable In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines harboring FLT3 N676D and Y842C in addition to FLT3 internal tandem duplications (ITD) in culture (PMID: 26822154). 26822154
FLT3 exon 14 ins FLT3 N676S FLT3 F691L Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/N676S mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L FLT3 D835E Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3 ITD with R834Q and F691L were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 mutant acute myeloid leukemia sensitive Cytarabine + Daunorubicin + Midostaurin FDA approved Actionable In a Phase III trial that supported FDA approval, treatment with Rydapt (midostaurin), combined with Cytosar-U (cytarabine) and Daunorubicin, improved overall survival (HR=0.78, p=0.009) and event-free survival (HR=0.78, p=0.002) in patients with FLT3-mutant or FLT3-ITD acute myeloid leukemia compared to Cytosar-U (cytarabine) and Daunorubicin with placebo (PMID: 28644114; NCT00651261). 28644114
FLT3 mutant acute myeloid leukemia sensitive Cytarabine + Daunorubicin + Midostaurin Phase Ib/II Actionable In a Phase Ib clinical trial, Rydapt (midostaurin) treatment after Daunorubicin and Cytosar-U (cytarabine) induction resulted in complete remission in 92% (12/13) of acute myeloid leukemia patients carrying FLT3 mutations, although overall survival rate was similar to patients with wild-type FLT3 (PMID: 22627678). 22627678
FLT3 mutant acute myeloid leukemia sensitive Selinexor + Sorafenib Phase Ib/II Actionable In a Phase I/II trial, combination of Selinexor and Nexavar (sorafenib) treatment resulted in complete remission in 29% (4/14) and more than 50% blast reduction in 14% (2/14) of patients with acute myeloid leukemia harboring FLT3 ITD and/or D835 mutations (ASH, 59th Annual Meeting and Exposition, Dec 2017, Abstract 1344; NCT01607892). detail...
FLT3 mutant acute myeloid leukemia predicted - sensitive Gilteritinib Phase Ib/II Actionable In a Phase I/II trial, treatment with Gilteritinib (ASP2215) resulted in an overall response rate of 49% (93/191) in patients with relapsed or refractory acute myeloid leukemia harboring FLT3 mutations, compared to 12% (7/58) in patients with wild-type FLT3 (PMID: 28645776; NCT02014558). detail... 28645776
FLT3 mutant acute myeloid leukemia sensitive E6201 Preclinical Actionable In a preclinical study, acute myeloid leukemia cell lines harboring FLT3 mutations demonstrated increased sensitivity to E6201 induced growth inhibition and apoptosis in culture compared to FLT3 wild-type cells (PMID: 26822154). 26822154
FLT3 mutant acute myeloid leukemia sensitive Crenolanib Phase I Actionable In a Phase I trial, Crenolanib treatment resulted in complete response (CR) in 39% (7/18), partial response (PR) in 11% (2/18), and an overall survival (OS) of 234 days in AML patients harboring FLT3 mutations (D835X, ITD, or both) that received no prior therapy, and CR in 17% (6/36), PR in 14% (5/36), and OS of 94 days in those progressed on TKIs (J Clin Oncol 34, 2016 (suppl; abstr 7008)). detail...
FLT3 mutant acute myeloid leukemia predicted - sensitive Cytarabine + Venetoclax Phase Ib/II Actionable In a Phase I/II trial, Venclexta (venetoclax) in combination with low-dose cytarabine resulted in complete remission or complete remission with incomplete count recovery in 44% (7/16) of patients with acute myeloid leukemia harboring FLT3 mutations who were ineligible for intensive chemotherapy (ASH Annual Meeting, Dec 2018, Abstract 284; NCT02287233). detail...
FLT3 mutant acute myeloid leukemia sensitive TG02 Preclinical - Cell line xenograft Actionable In a preclinical study, TG02 inhibited growth of FLT3-mutated acute myeloid leukemia cells in culture, resulted in complete tumor regression in cell line xenograft animal models (PMID: 21860433). 21860433
FLT3 mutant acute myeloid leukemia sensitive UNC2025 Preclinical Actionable In a preclinical study, UNC2025 inhibited FLT3 activation and growth of acute myeloid leukemia cells harboring a FLT3-ITD mutation in culture (PMID: 25068800). 25068800
FLT3 mutant acute myeloid leukemia sensitive Azacitidine + Midostaurin Phase Ib/II Actionable In a Phase Ib/II trial, acute myeloid leukemia patients harboring a FLT3 mutation demonstrated an improved remission duration when treated with the combination therapy, Rydapt (midostaurin) and Vidaza (azacitidine) (PMID: 25530214). 25530214
DNMT3A mut FLT3 mut NPM1 mut acute myeloid leukemia not applicable N/A Clinical Study Emerging In a retrospective analysis, the combination of DNMT3A, FLT3, and NPM1 mutations in patients with acute myeloid leukemia was highly associated with decreased event-free survival and overall survival, suggesting that this combination profile may serve as a future prognostic biomarker (PMID: 25281355). 25281355
FLT3 L611_E612insCSSDNEYFYVDFREYEYDLKWEFPRENL acute myeloid leukemia sensitive Tandutinib Preclinical Actionable In a preclinical study, tandutinib (CT53518) inhibited proliferation of cells expressing FLT3 L611_E612insCSSDNEYFYVDFREYEYDLKWEFPRENL in culture (PMID: 12124172). 12124172
FLT3 D835Y FLT3 N676D hematologic cancer sensitive G-749 Preclinical - Cell culture Actionable In a preclinical study, cells co-expressing FLT3 D835Y and FLT3 N676D were sensitive to G-749 in culture, demonstrating inhibition of cell growth and inhibition of Flt3 autophosphorylation (PMID: 22864397). 22864397
FLT3 D835Y hematologic cancer sensitive G-749 Preclinical - Cell culture Actionable In a preclinical study, cells expressing FLT3 D835Y were sensitive to G-749 in culture, demonstrating inhibition of cell growth and inhibition of Flt3 autophosphorylation (PMID: 22864397). 22864397
FLT3 D835Y acute myeloid leukemia sensitive E6201 Preclinical - Cell culture Actionable In a preclinical study, E6201 induced apoptosis in blast samples derived from acute myeloid leukemia patients harboring FLT3 D835Y in culture (PMID: 26822154). 26822154
FLT3 D835Y Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3 D835Y were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 D835Y Advanced Solid Tumor sensitive MRX-2843 Preclinical - Cell culture Actionable In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing FLT3 D835Y in culture (PMID: 27158668). 27158668
FLT3 D835Y acute promyelocytic leukemia sensitive Arsenic trioxide + Cytarabine + Methotrexate + Tretinoin Clinical Study Actionable In a clinical case study, a patient with acute promyelocytic leukemia harboring FLT3 D835Y demonstrated a complete molecular remission after treatment with Trisenox (arsenic trioxide) and Vesanoid (tretinoin) combined with Cytosar-U (cytarabine) and Methotrexate (PMID: 27626069). 27626069
FLT3 D835Y leukemia sensitive E6201 Preclinical Actionable In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines over expressing FLT3 D835Y in culture (PMID: 26822154). 26822154
FLT3 D835Y Advanced Solid Tumor sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, treatment with Rydapt (midostaurin) inhibited FLT3 phosphorylation and resulted in decreased proliferation and viability of transformed cells expressing FLT3 D835Y in culture (PMID: 12124173). 12124173
FLT3 D835Y acute promyelocytic leukemia resistant Tretinoin Clinical Study Actionable In a clinical case study, a patient with acute promyelocytic leukemia developed meningeal relapse after maintenance therapy with Vesanoid (tretinoid), which was found to be due to a FLT3 D835Y variant (PMID: 27626069). 27626069
FLT3 E598_Y599insGLVQVTGSSDNEYFYVDFREYE acute myeloid leukemia sensitive Tandutinib Preclinical Actionable In a preclinical study, tandutinib (CT53518) inhibited proliferation of cells expressing FLT3 E598_Y599insGLVQVTGSSDNEYFYVDFREYE in culture (PMID: 12124172). 12124172
FLT3 amp colorectal cancer sensitive Sorafenib Clinical Study Actionable In a clinical case report, Nexavar (sorafenib) treatment targeting FLT3 amplification in a rectal adenocarcinoma patient who had progressed on all standard therapies resulted in rapid clinical improvement (PMID: 25848357). 25848357
FLT3 positive acute myeloid leukemia not applicable AGS62P1 Preclinical - Patient cell culture Actionable In a preclinical study, AGS62P1 inhibited growth of FLT3-positive acute myeloid leukemia cell lines in culture, and led to tumor growth inhibition and regression in patient-derived xenograft (PDX) models (Blood 2015 126(23):3806). detail...
FLT3 Y842C acute myeloid leukemia sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) induced cell death and inhibited FLT3 activation and downstream STAT5 activation in primary acute myeloid leukemic blasts harboring FLT3 Y842C in culture (PMID: 15345593). 15345593
FLT3 Y842C acute myeloid leukemia resistant Imatinib Preclinical Actionable In a preclinical study, primary AML blasts expressing FLT3 Y842C were resistant to Gleevec (imatinib) as demonstrated by constitutively phosphorylated FLT3 and STAT-5 (PMID: 15345593). 15345593
FLT3 S451F Advanced Solid Tumor decreased response Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3 S451F demonstrated decreased sensitivity to inhibition of FLT3 phosphorylation and growth by Rydapt (midostaurin) in culture, when compared to cells expressing other FLT3 activating mutations (PMID: 18068628). 18068628
FLT3 D835H acute myeloid leukemia sensitive Crenolanib Preclinical Actionable In a preclinical study, Crenolanib (CP-868596) inhibited Flt3 phosphorylation and induced apoptosis in leukemia cells expressing FLT3 D835H (PMID: 24623852). 24623852
FLT3 D835V Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3 D835V were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 D835V Advanced Solid Tumor sensitive MRX-2843 Preclinical - Cell culture Actionable In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing FLT3 D835V in culture (PMID: 27158668). 27158668
FLT3 Y599_D600insSTDNEYFYVDFREYEY acute myeloid leukemia predicted - sensitive Quizartinib Phase I Actionable In a Phase I clinical trial, patients with refractory or relapsed acute myeloid leukemia positive for FLT3-ITD demonstrated a 53% (9/17) response rate compared to a 14% (5/37) response rate in those patients negative for FLT3-ITD when treated with Quizartinib (AC220) (PMID: 24002496). 24002496
FLT3 Y599_D600insSTDNEYFYVDFREYEY acute myeloid leukemia predicted - sensitive FLX925 Preclinical Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3-ITD secondary resistance mutation demonstrated sensitivity to FLX925 (Cancer Res, August 1, 2015 75; 787). detail...
FLT3 Y599_D600insSTDNEYFYVDFREYEY acute myeloid leukemia predicted - sensitive E6201 Preclinical - Cell line xenograft Actionable In a preclinical study, E6201 induced cell death, inhibited cell growth, and decreased tumor burden in acute myeloid leukemia cells harboring FLT3-ITD mutations in culture and in cell line xenograft models (Blood Nov 2013, 122 (21) 2683). detail...
FLT3 Y599_D600insSTDNEYFYVDFREYEY acute myeloid leukemia predicted - sensitive Azacitidine + Sorafenib Phase II Actionable In a Phase II trial, 93% (40/43) of acute myeloid leukemia patients harbored a FLT3-ITD and of the 37 patients that were evaluable, the combination therapy, Nexavar (sorafenib) and Vidaza (azacitidine), resulted in a 46% (17/37) response rate, which included 10 CRi, 6 CR, and 1 PR (PMID: 23613521). 23613521
IDH2 R140W FLT3 Y599_D600insSTDNEYFYVDFREYEY acute myeloid leukemia predicted - sensitive Enasidenib + Quizartinib Preclinical Actionable In a preclinical study, the combination of Enasidenib (AG-221) and Quizartinib (AC220) stimulated leukemic cell differentiation and reduced leukemic cell self-renewal in an acute myeloid leukemia mouse model simultaneously expressing IDH2 R140Q and a FLT3-ITD mutation (Blood Dec 2014, 124 (21) 437). detail...
FLT3 Y572C Advanced Solid Tumor sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited FLT3 phosphorylation of ERK1/2 and reduced cell growth in transformed cells expressing FLT3 Y572C in culture (PMID: 18068628). 18068628
FLT3 wild-type acute myeloid leukemia sensitive Cytarabine + Daunorubicin + Midostaurin Phase Ib/II Actionable In a Phase Ib clinical trial, Rydapt (midostaurin) treatment after Daunorubicin and Cytosar-U (cytarabine) induction resulted in complete remission in 74% (20 of 27) of acute myeloid leukemia patients carrying wild-type FLT3 (PMID: 22627678). 22627678
FLT3 wild-type acute myeloid leukemia sensitive Palbociclib Preclinical Actionable In a preclinical study, Ibrance (palbociclib) inhibited growth of human FLT3 wild-type human leukemia cells in culture (PMID: 27099147). 27099147
FLT3 wild-type acute myeloid leukemia sensitive TCS 359 Preclinical Actionable In a preclinical study, TCS-359 inhibited growth of FLT3 wild-type acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147
FLT3 wild-type acute myeloid leukemia sensitive Palbociclib + TCS 359 Preclinical Actionable In a preclinical study, Ibrance (palbociclib) following TCS-359 treatment enhanced growth inhibition of FLT3 wild-type acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147
FLT3 wild-type acute myeloid leukemia predicted - sensitive CG'806 Preclinical - Cell culture Actionable In a preclinical study, CG'806 inhibited Btk and aurora kinase activation, induced G2/M arrest and autophagy in acute myeloid leukemia cells harboring wild-type FLT3 in culture (Blood 2017 130:4629). detail...
FLT3 wild-type Advanced Solid Tumor sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited FLT3 phosphorylation in transformed cells expressing wild-type FLT3 in culture (PMID: 12124173). 12124173
FLT3 D835X acute myeloid leukemia sensitive Crenolanib Phase I Actionable In a Phase I trial, Crenolanib treatment resulted in an overall survival (OS) of 185 days in AML patients harboring FLT3 D835X that received no prior therapy (J Clin Oncol 34, 2016 (suppl; abstr 7008)). detail...
FLT3 D835X acute myeloid leukemia sensitive Selinexor + Sorafenib Phase Ib/II Actionable In a Phase I/II trial, combination of Selinexor and Nexavar (sorafenib) treatment resulted in complete remission in 29% (4/14) and more than 50% blast reduction in 14% (2/14) of patients with acute myeloid leukemia harboring FLT3 ITD and/or D835 mutations (ASH, 59th Annual Meeting and Exposition, Dec 2017, Abstract 1344; NCT01607892). detail...
FLT3 I836del cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited phosphorylation of FLT3, ERK, and STAT5, and growth of transformed cells expressing FLT3 I836del in culture (PMID: 17827387). 17827387
FLT3 I836del cancer sensitive Tandutinib Preclinical - Cell culture Actionable In a preclinical study, Tandutinib (CT53518) inhibited phosphorylation of FLT3 and activation of ERK and STAT5, and reduced growth of transformed cells expressing FLT3 I836del in culture (PMID: 15256420). 15256420
FLT3 D835G acute myeloid leukemia sensitive E6201 Preclinical - Cell culture Actionable In a preclinical study, E6201 induced apoptosis in blast samples derived from acute myeloid leukemia patients harboring FLT3 D835G in culture (PMID: 26822154). 26822154
FLT3 D835G leukemia sensitive E6201 Preclinical Actionable In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines over expressing FLT3 D835G in culture (PMID: 26822154). 26822154
FLT3 R595_L601dup acute myeloid leukemia sensitive Tandutinib Preclinical Actionable In a preclinical study, tandutinib (CT53518) inhibited cell proliferation in cell culture and in mouse models carrying FLT3 L601_K602insREYEYDL (PMID: 12124172). 12124172
FLT3 E612_F613insGYVDFREYEYDLKWEFRPRENLEF acute myeloid leukemia sensitive Tandutinib Preclinical Actionable In a preclinical study, tandutinib (CT53518) inhibited proliferation of cells expressing FLT3 E612_F613insGYVDFREYEYDLKWEFRPRENLEF in culture (PMID: 12124172). 12124172
FLT3 R834Q Advanced Solid Tumor sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited FLT3-induced phosphorylation of ERK1/2 and reduced growth of transformed cells expressing FLT3 R834Q in culture (PMID: 18068628). 18068628
FLT3 R834Q Advanced Solid Tumor sensitive PD98059 Preclinical Actionable In a preclinical study, PD98059 inhibited ERK1/2 phosphorylation and reduced cell growth in transformed cells expressing FLT3 R834Q (PMID: 18068628). 18068628
FLT3 Y599_D600insGLYVDFREYEY acute myeloid leukemia sensitive Tandutinib Preclinical Actionable In a preclinical study, tandutinib (CT53518) inhibited proliferation of cells expressing FLT3 Y599_D600insGLYVDFREYEY in culture (PMID: 12124172). 12124172
FLT3 act mut acute myeloid leukemia sensitive Gilteritinib FDA approved Actionable In a Phase III trial (ADMIRAL) that supported FDA approval, Xospata (gilteritinib) treatment resulted in complete remission (CR) or CR with partial hematologic recovery in 21% (29/138) of patients with relapsed or refractory acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD), D835, or I836 mutation (FDA.gov; NCT02421939). detail...
FLT3 act mut acute myeloid leukemia sensitive Palbociclib + Quizartinib Preclinical Actionable In a preclinical study, Ibrance (palbociclib) and Quizartinib (AC220) were synergistic towards growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147
FLT3 act mut acute myeloid leukemia sensitive VS-5584 Preclinical - Cell line xenograft Actionable In a preclinical study, VS-5584 inhibited PI3K/mTOR signaling and cell proliferation in a FLT3-ITD positive human acute myeloid leukemia cell line in culture, and inhibited tumor growth in xenograft models (PMID: 23270925). 23270925
FLT3 act mut acute myeloid leukemia sensitive Palbociclib + SGI-1776 Preclinical Actionable In a preclinical study, Ibrance (palbociclib) and SGI-1776 were synergistic towards growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147
FLT3 act mut acute myeloid leukemia sensitive TCS 359 Preclinical Actionable In a preclinical study, TCS-359 inhibited growth of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147
FLT3 act mut acute myeloid leukemia sensitive Sunitinib + Cytarabine + Daunorubicin Phase Ib/II Actionable In a Phase Ib/II trial, 59% (13/22) of acute myeloid leukemia patients harboring FLT3 activating mutations achieved complete remission following treatment with Sutent (sunitinib) in combination with Cytarabine and Daunorubicin (PMID: 25818407). 25818407
FLT3 act mut acute myeloid leukemia sensitive Palbociclib + Tandutinib Preclinical Actionable In a preclinical study, Ibrance (palbociclib) and tandutinib (MLN518) were synergistic towards growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147
FLT3 act mut acute myeloid leukemia sensitive Crenolanib Phase II Actionable In a Phase II trial, relapsed or refractory acute myeloid leukemia patients harboring FLT3 activating mutations without a history of FLT3 therapy demonstrated a significantly greater overall survival and event free survival compared to those that had prior FLT3 therapy when treated with Crenolanib (ASH meeting, Dec 2014, abstract #389). detail...
FLT3 act mut acute myeloid leukemia sensitive Palbociclib Preclinical Actionable In a preclinical study, Ibrance (palbociclib) blocked growth, induced apoptosis, and inhibited STAT activation in human FLT3-ITD positive human acute myeloid leukemia cells in culture (PMID: 27099147). 27099147
FLT3 act mut leukemia sensitive Pexidartinib Preclinical - Cell line xenograft Actionable In a preclinical study, PLX3397 inhibited FLT3 autophosphorylation in leukemia cells overexpressing FLT3 or harboring FLT3 activating mutations, and inhibited growth of leukemia cells harboring FLT3-ITD mutations in culture and in cell line xenograft models (ASH Annual Meeting Abstracts 2011 118: 3632). detail...
FLT3 act mut acute myeloid leukemia sensitive Palbociclib + TCS 359 Preclinical Actionable In a preclinical study, Ibrance (palbociclib) following TCS-359 treatment enhanced growth inhibition of FLT3-ITD positive acute myeloid leukemia cell lines in culture (PMID: 27099147). 27099147