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Gene FLT3
Variant Y597_K602dup
Impact List duplication
Protein Effect gain of function - predicted
Gene Variant Descriptions 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).
Associated Drug Resistance

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Transcript NM_004119
gDNA chr13:g.28034112_28034113insCTTAAGGTCATACTCATA
cDNA c.1807_1808insATGAGTATGACCTTAAGT
Protein p.Y597_K602dupYEYDLK
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004119 chr13:g.28034112_28034113insCTTAAGGTCATACTCATA c.1807_1808insATGAGTATGACCTTAAGT p.Y597_K602dupYEYDLK RefSeq GRCh38/hg38

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  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
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  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 exon 14 ins hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Quizartinib (AC220) inhibited growth of transformed hematologic cells expressing FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). 31309543
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 myelodysplastic syndrome not applicable N/A Guideline Prognostic FLT3 internal tandem duplication (FLT3-ITD) mutations are associated with poor prognosis in patients with myelodysplastic syndrome (NCCN.org). detail...
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 B-cell acute lymphoblastic leukemia predicted - sensitive CD19/CD22 CAR T cells Case Reports/Case Series Actionable In a clinical case study, CD19/CD22 CAR T cell treatment resulted in rapid and durable suppression of leukemia cells in a patient with refractory acute B-cell lymphoblastic leukemia harboring a FLT3 internal tandem duplication (ITD) mutation (PMID: 32005917). 32005917
FLT3 exon 14 ins acute myeloid leukemia sensitive A-1210477 + Venetoclax Preclinical - Cell culture Actionable In a preclinical study, A-1210477 and Venclexta (venetoclax) combination treatment synergistically inhibited viability of acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins acute myeloid leukemia sensitive PD-0325901 + Sorafenib Preclinical - Patient cell culture Actionable In a preclinical study, Nexavar (sorafenib) and PD-0325901 synergistically induced apoptosis and inhibited proliferation of acute myeloid leukemia (AML) cell lines harboring FLT3 internal tandem duplication (ITD) mutations in culture, inhibited Erk phosphorylation in FLT3-ITD mutant AML patient cells, and reduced leukemic burden in a FLT3-ITD mutant AML cell line xenograft model (PMID: 28923853). 28923853
FLT3 exon 14 ins acute myeloid leukemia 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 MK2206 + Palbociclib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Ibrance (palbociclib) and MK2206 resulted in a synergistic effect in acute myeloid leukemia cells expressing a FLT3-ITD, demonstrating a greater reduced cell viability compared to either agent alone (PMID: 30544932). 30544932
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 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 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 LAM-003 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3 internal tandem duplication (ITD) demonstrated sensitivity to LAM-003 treatment in culture (PMID: 31751472). 31751472
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 acute myeloid leukemia sensitive LAM-003 + Tazemetostat Preclinical - Cell culture Actionable In a preclinical study, LAM-003 and Tazemetostat (EPZ-6438) combination treatment synergistically inhibited viability of acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins acute myeloid leukemia sensitive UNC1666 Preclinical - Cell culture Actionable In a preclinical study, UNC1666 inhibited FLT3 phosphorylation and downstream signaling, induced apoptosis of acute myeloid leukemia cells harboring FLT3 exon 14 insertions (ITD) in culture (PMID: 25762638). 25762638
FLT3 exon 14 ins acute myeloid leukemia sensitive CCT137690 + Palbociclib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Ibrance (palbociclib) and CCT137690 resulted in a synergistic effect in acute myeloid leukemia cells harboring a FLT3-ITD, demonstrating a greater reduced cell viability compared to either agent alone (PMID: 30544932). 30544932
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 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 acute myeloid leukemia sensitive Sorafenib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Nexavar (sorafenib) combined with Mekinist (trametinib) enhanced apoptosis in acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) mutations in culture (PMID: 28923853). 28923853
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 acute myeloid leukemia sensitive Cytarabine + Daunorubicin + Midostaurin FDA approved - On Companion Diagnostic 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 (D835X and I836X) or FLT3-ITD (exon 14 insertions) acute myeloid leukemia compared to Cytosar-U (cytarabine) and Daunorubicin with placebo (PMID: 28644114). 28644114 detail... detail...
FLT3 exon 14 ins acute myeloid leukemia sensitive Alisertib + Palbociclib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Ibrance (palbociclib) and Alisertib (MLN8237) resulted in a synergistic effect in acute myeloid leukemia cells expressing a FLT3-ITD, demonstrating a greater reduced cell viability compared to either agent alone (PMID: 30544932). 30544932
FLT3 exon 14 ins acute myeloid leukemia sensitive Daunorubicin + LAM-003 Preclinical - Cell culture Actionable In a preclinical study, LAM-003 and Cerubidine (daunorubicin) combination treatment synergistically reduced viability of acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive Ibrutinib Preclinical - Patient cell culture Actionable In a preclinical study, FLT3-ITD mutations correlated with sensitivity to Imbruvica (ibrutinib) in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). 30333627
FLT3 exon 14 ins acute myeloid leukemia sensitive Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Nexavar (sorafenib) inhibited Flt3 phosphorylation and growth of acute myeloid leukemia cell lines harboring FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). 31309543
FLT3 exon 14 ins acute myeloid leukemia sensitive Sorafenib Preclinical - Patient cell culture Actionable In a preclinical study, FLT3-ITD mutations correlated with sensitivity to Nexavar (sorafenib) in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). 30333627
FLT3 exon 14 ins hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib inhibited growth of transformed hematologic cells expressing FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). 31309543
FLT3 exon 14 ins hematologic cancer sensitive KW-2449 Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD were sensitive to treatment with KW-2449, demonstrating growth inhibition in culture (PMID: 22858906). 22858906
FLT3 exon 14 ins acute myeloid leukemia sensitive CG-806 Preclinical - Cell line xenograft Actionable In a preclinical study, CG-806 inhibited FLT3 downstream signaling, resulted in growth inhibition of acute myeloid leukemia cells harboring FLT3 exon 14 insertion (ITD) in culture and tumor inhibition in cell line xenograft models (Clin Cancer Res 2017; 23(24_Suppl):Abstract nr 25). detail... detail...
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 sensitive MK2206 + Venetoclax Preclinical - Cell culture Actionable In a preclinical study, MK2206 and Venclexta (venetoclax) combination treatment synergistically induced cell death of acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). 31751472
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 hematologic cancer sensitive HQP1351 Preclinical - Cell culture Actionable In a preclinical study, GZD824 (HQP1351) inhibited growth of transformed cells expressing FLT3-ITD in culture (PMID: 32247263). 32247263
FLT3 exon 14 ins acute myeloid leukemia resistant Avapritinib Preclinical - Cell culture Actionable In a preclinical study, Ayvakit (avapritinib) did not inhibit Flt3 phosphorylation or growth of acute myeloid leukemia cell lines harboring FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). 31309543
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 hematologic cancer decreased response Avapritinib Preclinical - Cell culture Actionable In a preclinical study, Ayvakit (avapritinib) inhibited growth of transformed hematologic cells expressing FLT3 exon 14 insertions (ITD) in culture with reduced potency compared to other kinase inhibitors (PMID: 31309543). 31309543
FLT3 exon 14 ins Advanced Solid Tumor sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3 internal tandem duplication (ITD) demonstrated sensitivity to Crenolanib treatment in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins acute myeloid leukemia sensitive FLT3/CD3 Fabsc antibody Preclinical - Cell culture Actionable In a preclinical study, treatment of an acute myeloid leukemia (AML) cell lines or patient-derived xenograft (PDX)-derived AML cells harboring a heterozygous FLT3-ITD mutation with a Fabsc FLT3/CD3 bi-specific antibody resulted in near complete eradication of AML cells in culture (PMID: 28895560). 28895560
FLT3 exon 14 ins hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited growth of transformed hematologic cells expressing FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). 31309543
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 hematologic cancer sensitive Palbociclib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3 ITD were sensitive to treatment with Ibrance (palbociclib), demonstrating inhibition of cell growth in culture (PMID: 30544932). 30544932
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 LAM-003 Preclinical - Patient cell culture Actionable In a preclinical study, LAM-003 treatment inhibited colony formation, and reduced viability of acute myeloid cell lines harboring FLT3 internal tandem duplication (ITD) in the presence of stromal factors that confer resistance to Xospata (gilteritinib) and Crenolanib, and induced apoptosis in patient-derived cells in culture, and induced tumor regression, and increased survival in cell line xenograft models (PMID: 31751472). 31751472
FLT3 exon 14 ins acute myeloid leukemia sensitive Ipatasertib + Palbociclib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Ibrance (palbociclib) and Alisertib (MLN8237) resulted in a synergistic effect in acute myeloid leukemia cells expressing a FLT3-ITD, demonstrating a greater reduced cell viability compared to either agent alone (PMID: 30544932). 30544932
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 Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib inhibited Flt3 phosphorylation and growth of acute myeloid leukemia cell lines harboring FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). 31309543
FLT3 exon 14 ins acute myeloid leukemia sensitive Crenolanib Preclinical - Patient cell culture Actionable In a preclinical study, FLT3-ITD mutations correlated with sensitivity to Crenolanib in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). 30333627
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 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 sensitive GSK690693 + Venetoclax Preclinical - Cell culture Actionable In a preclinical study, GSK690693 and Venclexta (venetoclax) combination treatment synergistically induced cell death of acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins acute myeloid leukemia conflicting Midostaurin Preclinical - Cell culture Actionable In a preclinical study, co-culturing human stromal cells with an acute myeloid cell line harboring a FLT3 internal tandem duplication (ITD) demonstrated resistance to Rydapt (midostaurin) treatment in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins acute myeloid leukemia conflicting Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) inhibited Flt3 phosphorylation and growth of acute myeloid leukemia cell lines harboring FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). 31309543
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 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 acute myeloid leukemia sensitive Tandutinib Preclinical - Cell culture Actionable In a preclinical study, Tandutinib (CT53518) treatment inhibited viability of an acute myeloid leukemia cell line harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). 31751472
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 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 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 sensitive Gilteritinib + LAM-003 Preclinical - Cell culture Actionable In a preclinical study, LAM-003 and Xospata (gilteritinib) combination treatment reduced viability of acute myeloid leukemia cell lines harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). 31751472
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive Pexidartinib Phase Ib/II Actionable In a Phase I/II trial, treatment with Turalio (pexidartinib) was well-tolerated and resulted in an overall response rate of 21% (19/90) and a composite complete remission (CRc) rate of 11% (10/90) in patients with relapsed/refractory acute myeloid leukemia harboring a FLT3-ITD mutation (PMID: 32330242; NCT01349049). 32330242
FLT3 exon 14 ins acute myeloid leukemia 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 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 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 sensitive HQP1351 Preclinical - Cell line xenograft Actionable In a preclinical study, GZD824 (HQP1351) reduced Flt3 and Stat5 phosphorylation, induced cell cycle arrest and apoptosis, and inhibited growth of acute myeloid leukemia cells harboring FLT3-ITD in culture, and suppressed tumor growth, decreased Flt3 activation, and induced apoptosis in cell line xenograft models (PMID: 32247263). 32247263
FLT3 exon 14 ins hematologic cancer sensitive Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Nexavar (sorafenib) inhibited growth of transformed hematologic cells expressing FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). 31309543
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 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 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 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 LAM-003 + Venetoclax Preclinical - Patient cell culture Actionable In a preclinical study, LAM-003 and Venclexta (venetoclax) combination treatment synergistically induced cell death, and inhibited viability of acute myeloid leukemia cell lines and patient-derived cells harboring FLT3 internal tandem duplication (ITD) in culture, and increased survival in a cell line xenograft model (PMID: 31751472). 31751472
FLT3 exon 14 ins acute myeloid leukemia predicted - sensitive KW-2449 Preclinical - Patient cell culture Actionable In a preclinical study, FLT3-ITD mutations correlated with sensitivity to KW-2449 in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). 30333627
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 sensitive Gilteritinib FDA approved - On Companion Diagnostic 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; exon 14 insertion), D835, or I836 mutation (FDA.gov; NCT02421939). detail... detail...
FLT3 exon 14 ins acute myeloid leukemia sensitive Gilteritinib Guideline Actionable Xospata (gilteritinib) is included in the 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 A-419259 Preclinical - Cell culture Actionable In a preclinical study, A-419259 treatment inhibited viability of an acute myeloid leukemia cell line harboring FLT3-ITD in culture (PMID: 31790499). 31790499
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 acute myeloid leukemia sensitive Quizartinib Phase II Actionable In a Phase II trial, Quizartinib (AC220) treatment resulted in a composite complete remission (CCR) in 56% (63/112; 3 complete remission (CR)) of FLT3-ITD-positive patients vs. 36% (16/44; 1 CR) of FLT3-ITD-negative patients with relapsed/refractory acute myeloid leukemia (AML) after first-line therapy, and CCR in 46% (62/136; 5 CR) of FLT3-ITD-positive vs. 30% (12/40; 1 CR) in FLT3-ITD-negative patients with relapsed/refractory AML after salvage chemotherapy or transplant (PMID: 29859851; NCT00989261). 29859851
FLT3 exon 14 ins acute myeloid leukemia sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Quizartinib (AC220) inhibited Flt3 phosphorylation and growth of acute myeloid leukemia cell lines harboring FLT3_OT exon 14 insertions (ITD) in culture (PMID: 31309543). 31309543
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 sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Quizartinib (AC220) inhibited proliferation of several acute myeloid leukemia cell lines harboring different FLT3-ITD mutations in culture (PMID: 28895560). 28895560
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 acute myeloid leukemia predicted - sensitive Entospletinib Preclinical - Patient cell culture Actionable In a preclinical study, FLT3-ITD mutations correlated with sensitivity to Entospletinib in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). 30333627
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 hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited growth of transformed hematologic cells expressing FLT3 exon 14 insertions (ITD) in culture (PMID: 31309543). 31309543
FLT3 exon 14 ins acute myeloid leukemia sensitive Cytarabine + LAM-003 Preclinical - Cell culture Actionable In a preclinical study, LAM-003 and Cytosar-U (cytarabine) combination treatment synergistically reduced viability of an acute myeloid leukemia cell line harboring FLT3 internal tandem duplication (ITD) in culture (PMID: 31751472). 31751472
FLT3 exon14 acute myeloid leukemia sensitive Gilteritinib Guideline Actionable Xospata (gilteritinib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org). detail...
FLT3 exon14 acute myeloid leukemia sensitive Cytarabine + Daunorubicin + Midostaurin Guideline Actionable Rydapt (midostaurin), in combination with Cerubidine (daunorubicin) and Cytosar-U (cytarabine), is included in guidelines for patients with acute myeloid leukemia harboring a mutation in the FLT3 tyrosine kinase domain (exons 14-23) (NCCN.org). detail...
FLT3 mutant acute myeloid leukemia sensitive Zotiraciclib Preclinical - Cell line xenograft Actionable In a preclinical study, Zotiraciclib (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 Cytarabine + Venetoclax Guideline Actionable Venclexta (venetoclax) in combination with Cytosar-U (cytarabine) is included in guidelines for adult patients with acute myeloid leukemia harboring a FLT3 mutation (NCCN.org). detail...
FLT3 mutant acute myeloid leukemia 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 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 sensitive Gilteritinib FDA approved - Has Companion Diagnostic 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... detail...
FLT3 mutant acute myeloid leukemia 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 Decitabine + Venetoclax Guideline Actionable Venclexta (venetoclax) in combination with Dacogen (decitabine) is included in guidelines for adult patients with acute myeloid leukemia harboring a FLT3 mutation (NCCN.org). detail...
FLT3 mutant acute myeloid leukemia sensitive Cytarabine + Daunorubicin + Midostaurin FDA approved - Has Companion Diagnostic 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 (ITD, D835X, and I836X mutations) acute myeloid leukemia compared to Cytosar-U (cytarabine) and Daunorubicin with placebo (PMID: 28644114; NCT00651261). 28644114 detail... detail...
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 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 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
FLT3 mutant acute myeloid leukemia sensitive Azacitidine + Venetoclax Guideline Actionable Venclexta (venetoclax) in combination with Vidaza (azacitidine) is included in guidelines for adult patients with acute myeloid leukemia harboring a FLT3 mutation (NCCN.org). detail...
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 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 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 Cytarabine + Daunorubicin + Sunitinib 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 + 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 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 + 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 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 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 + 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
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...
Molecular Profile Protein Effect Treatment Approaches
FLT3 Y597_K602dup gain of function - predicted FLT3 Inhibitor