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Gene FLT3
Variant D835H
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions FLT3 D835H lies within the protein kinase domain activation loop of the Flt3 protein (PMID: 11290608). D835H results in constitutive phosphorylation of Flt3 and activation of Stat5, Erk signaling, leading to transformation of cultured cells (PMID: 15256420).
Associated Drug Resistance
Category Variants Paths

FLT3 mutant FLT3 exon20 FLT3 D835X FLT3 D835H

FLT3 mutant FLT3 act mut FLT3 D835H

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Transcript NM_004119.3
gDNA chr13:g.28018505C>G
cDNA c.2503G>C
Protein p.D835H
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004119.2 chr13:g.28018505C>G c.2503G>C p.D835H RefSeq GRCh38/hg38
NM_004119 chr13:g.28018505C>G c.2503G>C p.D835H RefSeq GRCh38/hg38
NM_004119.3 chr13:g.28018505C>G c.2503G>C p.D835H 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 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 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 acute myeloid leukemia sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of acute myeloid leukemia cells harboring FLT3-ITD and FLT3 D835H in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835H hematologic cancer sensitive Dubermatinib Preclinical - Cell culture Actionable In a preclinical study, Dubermatinib (TP-0903) inhibited growth of transformed cells expressing a FLT3-ITD mutation and FLT3 D835H in culture (PMID: 33268594). 33268594
FLT3 exon 14 ins FLT3 D835H hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835H in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835H hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) resulted in reduced cell viability in transformed cells expressing FLT3 ITD with FLT3 D835H in culture (PMID: 32040554). 32040554
FLT3 exon 14 ins FLT3 D835H hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835H in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835H acute myeloid leukemia sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) resulted in reduced cell viability in acute myeloid leukemia cells harboring FLT3 ITD with FLT3 D835H in culture (PMID: 32040554). 32040554
FLT3 exon 14 ins FLT3 D835H acute myeloid leukemia resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring FLT3 ITD with FLT3 D835H were resistant to Vanflyta (quizartinib) in culture (PMID: 32040554). 32040554
FLT3 exon 14 ins FLT3 D835H hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib (CP-868596) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835H in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835H hematologic cancer predicted - resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 D835H were moderately resistant to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835H hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835H in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835H acute myeloid leukemia resistant Sorafenib Preclinical - Cell line xenograft Actionable In a preclinical study, FLT3 D835H was identified as a secondary resistance mutation in FLT3 ITD-positive acute myeloid leukemia cell line xenograft models that progressed on Nexavar (sorafenib) (PMID: 35344039). 35344039
FLT3 exon 14 ins FLT3 D835H acute myeloid leukemia resistant Crenolanib Preclinical - Cell line xenograft Actionable In a preclinical study, FLT3 D835H was identified as a secondary resistance mutation in FLT3 ITD-positive acute myeloid leukemia cell line xenograft models that progressed on Crenolanib (CP-868596) (PMID: 35344039). 35344039
FLT3 exon 14 ins FLT3 D835H hematologic cancer sensitive Pacritinib Preclinical - Cell culture Actionable In a preclinical study, Vonjo (pacritinib) inhibited viability in a transformed cell line expressing a FLT3-ITD mutation and FLT3 D835H in culture (PMID: 31102119). 31102119
FLT3 exon 14 ins FLT3 D835H acute myeloid leukemia sensitive RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, RMC-4550 inhibited viability in an acute myeloid leukemia cell line harboring FLT3 ITD and expressing FLT3 D835H in culture (PMID: 37992684). 37992684
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