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Gene | FLT3 |
Variant | Y842C |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | FLT3 Y842C lies within the protein kinase domain of the Flt3 protein (UniProt.org). Y842C results in constitutive phosphorylation of Flt3, activation of Stat5 signaling, is transforming in cell culture (PMID: 15345593), and has been demonstrated to promote secondary drug resistance in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 22504184, PMID: 29187377). |
Associated Drug Resistance | Y |
Category Variants Paths |
FLT3 mutant FLT3 act mut FLT3 Y842C FLT3 mutant FLT3 exon20 FLT3 Y842C |
Transcript | NM_004119.3 |
gDNA | chr13:g.28018483T>C |
cDNA | c.2525A>G |
Protein | p.Y842C |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004119.2 | chr13:g.28018483T>C | c.2525A>G | p.Y842C | RefSeq | GRCh38/hg38 |
NM_004119.3 | chr13:g.28018483T>C | c.2525A>G | p.Y842C | RefSeq | GRCh38/hg38 |
NM_004119 | chr13:g.28018483T>C | c.2525A>G | p.Y842C | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FLT3 Y842C | hematologic cancer | sensitive | Foretinib | Preclinical - Cell culture | Actionable | In a preclinical study, Foretinib (GSK1363089) inhibited viability of cultured cells expressing FLT3 Y842C (PMID: 38231480). | 38231480 |
FLT3 Y842C | acute myeloid leukemia | resistant | Imatinib | Preclinical | Actionable | In a preclinical study, primary AML blasts expressing FLT3 Y842C were resistant to Gleevec (imatinib) as demonstrated by constitutively phosphorylated FLT3 and STAT-5 (PMID: 15345593). | 15345593 |
FLT3 Y842C | acute myeloid leukemia | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) induced cell death and inhibited FLT3 activation and downstream STAT5 activation in primary acute myeloid leukemic blasts harboring FLT3 Y842C in culture (PMID: 15345593). | 15345593 |
FLT3 Y842C | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, cultured cells expressing FLT3 Y842C were resistant to treatment with Vanflyta (quizartinib) (PMID: 38231480). | 38231480 |
FLT3 Y842C | hematologic cancer | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) inhibited viability of cultured cells expressing FLT3 Y842C (PMID: 38231480). | 38231480 |
FLT3 Y842C | hematologic cancer | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) resulted in reduced cell viability in transformed cells expressing FLT3 Y842C in culture (PMID: 32040554). | 32040554 |