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Gene | FLT3 |
Variant | D839G |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | FLT3 D839G lies within the protein kinase domain activation loop of the Flt3 protein (UniProt.org). D839G results in constitutive phosphorylation of Flt3, activation of Akt and Mapk signaling, leading to transformation of cultured cells (PMID: 24608088), and has been demonstrated to occur as a secondary resistance mutation in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 25847190). |
Associated Drug Resistance | Y |
Category Variants Paths |
FLT3 mutant FLT3 act mut FLT3 D839G FLT3 mutant FLT3 exon20 FLT3 D839G |
Transcript | NM_004119.3 |
gDNA | chr13:g.28018492T>C |
cDNA | c.2516A>G |
Protein | p.D839G |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004119 | chr13:g.28018492T>C | c.2516A>G | p.D839G | RefSeq | GRCh38/hg38 |
NM_004119.3 | chr13:g.28018492T>C | c.2516A>G | p.D839G | RefSeq | GRCh38/hg38 |
NM_004119.2 | chr13:g.28018492T>C | c.2516A>G | p.D839G | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FLT3 exon 14 ins FLT3 F691L FLT3 D839G | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a compound FLT3-ITD /F691L/D839G mutation were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
FLT3 exon 14 ins FLT3 D839G | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, FLT3 D839G conferred resistance to PLX3397 when expressed in a compound mutation with FLT3-ITD in cell culture (PMID: 25847190). | 25847190 |
FLT3 exon 14 ins FLT3 D839G | hematologic cancer | sensitive | Momelotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Momelotinib (CYT387) decreased phosphorylation of Flt3 and Stat5 and inhibited proliferation of transformed cells expressing FLT3-ITD and FLT3 D839G in culture (PMID: 34768286). | 34768286 |
FLT3 exon 14 ins FLT3 D839G | hematologic cancer | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) inhibited proliferation of transformed cells expressing FLT3-ITD and FLT3 D839G in culture (PMID: 34768286). | 34768286 |
FLT3 exon 14 ins FLT3 D839G | 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 D839G in culture (PMID: 32040554). | 32040554 |
FLT3 exon 14 ins FLT3 D839G | hematologic cancer | sensitive | Lestaurtinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lestaurtinib (CEP-701) inhibited proliferation of transformed cells expressing FLT3-ITD and FLT3 D839G in culture (PMID: 34768286). | 34768286 |
FLT3 exon 14 ins FLT3 D839G | hematologic cancer | resistant | Sorafenib | Preclinical - Biochemical | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 D839G demonstrated resistance to Nexavar (sorafenib) in culture (PMID: 34768286). | 34768286 |
FLT3 exon 14 ins FLT3 D839G | hematologic cancer | resistant | Pacritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 D839G demonstrated resistance to Vonjo (pacritinib) in culture (PMID: 34768286). | 34768286 |
FLT3 exon 14 ins FLT3 D839G | hematologic cancer | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 D839G were sensitive to Rydapt (midostaurin) treatment in culture (PMID: 34768286). | 34768286 |
FLT3 exon 14 ins FLT3 D839G | hematologic cancer | sensitive | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 D839G were sensitive to Crenolanib (CP-868596) treatment in culture (PMID: 34768286). | 34768286 |