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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 |
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 |
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 |