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Gene FLT3
Variant D835N
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions FLT3 D835N lies within the protein kinase domain activation loop of the Flt3 protein (PMID: 11290608). D835N results in constitutive phosphorylation of Flt3 and activation of Stat5, Erk signaling, leading to transformation of cultured cells (PMID: 15256420).
Associated Drug Resistance

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Transcript NM_004119
gDNA chr13:g.28018505C>T
cDNA c.2503G>A
Protein p.D835N
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004119 chr13:g.28018505C>T c.2503G>A p.D835N RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 exon 14 ins FLT3 D835N hematologic cancer sensitive HQP1351 Preclinical - Cell culture Actionable In a preclinical study, GZD824 (HQP1351) inhibited growth of transformed cells expressing FLT3-ITD and FLT3 D835N in culture (PMID: 32247263). 32247263
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 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
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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 + 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 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 + 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 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 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 + 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 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 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 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 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 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 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 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 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 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 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 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 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 D835X myelodysplastic syndrome not applicable N/A Guideline Prognostic FLT3 D835 mutations are associated with poor prognosis in patients with myelodysplastic syndromes (NCCN.org). detail...
FLT3 D835X 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). detail... 28644114 detail...
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 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), D835, or I836 mutation (FDA.gov; NCT02421939). detail... detail...
FLT3 D835X acute myeloid leukemia predicted - sensitive LAM-003 Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived acute myeloid leukemia cells harboring FLT3 D835X demonstrated sensitivity to LAM-003 treatment in culture (PMID: 31751472). 31751472
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 exon20 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 exon20 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...
Molecular Profile Protein Effect Treatment Approaches
FLT3 D835N gain of function FLT3 Inhibitor
FLT3 exon 14 ins FLT3 D835N
FLT3 exon 14 ins FLT3 F691L FLT3 D835N