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Gene FLT3
Variant D835F
Impact List missense
Protein Effect unknown
Gene Variant Descriptions FLT3 D835F lies within the activation loop in the protein kinase domain of the Flt3 protein (PMID: 25837374). D835F has been associated with FLT3 inhibitor resistance (PMID: 24227820, PMID: 23430109), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Oct 2023).
Associated Drug Resistance Y
Category Variants Paths

FLT3 mutant FLT3 exon20 FLT3 D835X FLT3 D835F

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Transcript NM_004119.3
gDNA chr13:g.28018504_28018505delGAinsTT
cDNA c.2503_2504delGAinsTT
Protein p.D835F
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004119.2 chr13:g.28018504_28018505delGAinsTT c.2503_2504delGAinsTT p.D835F RefSeq GRCh38/hg38
NM_004119.3 chr13:g.28018504_28018505delGAinsTT c.2503_2504delGAinsTT p.D835F RefSeq GRCh38/hg38
NM_004119 chr13:g.28018504_28018505delTCinsAA c.2503_2504delGAinsTT p.D835F 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 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 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 acute myeloid leukemia predicted - resistant Sorafenib Case Reports/Case Series Actionable In a clinical case study, FLT3 D835F was identified as an acquired resistance mutation in a patient with acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD) whose disease progressed on Nexavar (sorafenib) after initial response (PMID: 24227820). 24227820
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 hematologic cancer sensitive KX2-391 Preclinical - Cell culture Actionable In a preclinical study, KX2-391 treatment inhibited cell viability and decreased downstream signaling in cells expressing a FLT3-ITD mutation with FLT3 D835F in culture (PMID: 34217323). 34217323
FLT3 exon 14 ins FLT3 D835F 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 D835F in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835F 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 D835F in culture (PMID: 32040554). 32040554
FLT3 exon 14 ins FLT3 D835F 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 D835F in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835F 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 D835F in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835F hematologic cancer resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 D835F were resistant to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835F 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 D835F in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835F hematologic cancer resistant Sitravatinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation with FLT3 D835F were resistant to treatment with Sitravatinib (MGCD516) in culture (PMID: 36691065). 36691065