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Gene | FLT3 |
Variant | A848P |
Impact List | missense |
Protein Effect | gain of function - predicted |
Gene Variant Descriptions | FLT3 A848P lies within the protein kinase domain of the Flt3 protein (UniProt.org). A848P results in growth factor independent cell proliferation, Flt3 phosphorylation, and Erk activation in culture (Blood; 2009, 114;22, Abstract #3982), and has been demonstrated to confer resistance to FLT3 inhibitors in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations in culture (PMID: 20520641), and therefore, is predicted to lead to a gain of Flt3 protein function. |
Associated Drug Resistance | Y |
Category Variants Paths |
FLT3 mutant FLT3 act mut FLT3 A848P FLT3 mutant FLT3 exon21 FLT3 A848P |
Transcript | NM_004119.3 |
gDNA | chr13:g.28015701C>G |
cDNA | c.2542G>C |
Protein | p.A848P |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004119 | chr13:g.28015701C>G | c.2542G>C | p.A848P | RefSeq | GRCh38/hg38 |
NM_004119.3 | chr13:g.28015701C>G | c.2542G>C | p.A848P | RefSeq | GRCh38/hg38 |
NM_004119.2 | chr13:g.28015701C>G | c.2542G>C | p.A848P | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FLT3 exon 14 ins FLT3 A848P | Advanced Solid Tumor | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and A848P were resistant to Sutent (sunitinib) in culture (PMID: 23392356). | 23392356 |
FLT3 exon 14 ins FLT3 A848P | Advanced Solid Tumor | decreased response | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and A848P demonstrated reduced sensitivity to Nexavar (sorafenib) in culture (PMID: 23392356). | 23392356 |
FLT3 exon 14 ins FLT3 A848P | Advanced Solid Tumor | decreased response | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and A848P demonstrated reduced sensitivity to Vanflyta (quizartinib) in culture (PMID: 23392356). | 23392356 |
FLT3 exon 14 ins FLT3 A848P | acute myeloid leukemia | predicted - sensitive | FF-10101 | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring FLT3-ITD and FLT3 A848P demonstrated sensitivity to treatment with FF-10101 in culture (PMID: 35395091). | 35395091 |
FLT3 exon 14 ins FLT3 A848P | 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 A848P in culture (PMID: 32040554). | 32040554 |
FLT3 exon 14 ins FLT3 A848P | hematologic cancer | resistant | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FLT3-ITD with FLT3 A848P were resistant to Nexavar (sorafenib) in culture (PMID: 20520641). | 20520641 |
FLT3 exon 14 ins FLT3 A848P | hematologic cancer | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FLT3-ITD with FLT3 A848P were resistant to Sutent (sunitinib) in culture (PMID: 20520641). | 20520641 |
FLT3 exon 14 ins FLT3 A848P | hematologic cancer | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) treatment inhibited growth of cells expressing FLT3-ITD with FLT3 A848P in culture (PMID: 20520641). | 20520641 |
FLT3 exon 14 ins FLT3 A848P | chronic myelomonocytic leukemia | predicted - resistant | Sorafenib + Sunitinib | Case Reports/Case Series | Actionable | In a clinical case study, FLT3 A848P was identified after progression on the alternating treatment of Nexvar (sorafenib) and Sutent (sunitinib) in a patient with chronic myelomoncytic leukemia harboring a FLT3-ITD mutation (PMID: 20520641). | 20520641 |