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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 | 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_004119.2 | 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 exon 14 ins FLT3 Y842C | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, FLT3 Y842C conferred resistance to PLX3397 when expressed in a compound mutation with FLT3-ITD in cell culture (PMID: 25847190). | 25847190 |
FLT3 exon 14 ins FLT3 Y842C | leukemia | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines harboring FLT3 Y842C in addition to FLT3 internal tandem duplications (ITD) in culture (PMID: 26822154). | 26822154 |
FLT3 exon 14 ins FLT3 Y842C | 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 Y842C in culture (PMID: 27158668). | 27158668 |
FLT3 exon 14 ins FLT3 Y842C | acute myeloid leukemia | resistant | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 Y842C demonstrated resistance to Sutent (sunitinib) in culture (Blood 2009 114:3776). | detail... |
FLT3 exon 14 ins FLT3 Y842C | acute myeloid leukemia | resistant | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 Y842C demonstrated resistance to Nexavar (sorafenib) in culture (Blood 2009 114:3776). | detail... |
FLT3 exon 14 ins FLT3 Y842C | acute myeloid leukemia | resistant | AGL2043 | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 Y842C demonstrated resistance to AGL2043 in culture (Blood 2009 114:3776). | detail... |
FLT3 exon 14 ins FLT3 Y842C | acute myeloid leukemia | sensitive | Lestaurtinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 Y842C demonstrated sensitivity to Lestaurtinib (CEP-701) in culture (Blood 2009 114:3776). | detail... |
FLT3 exon 14 ins FLT3 Y842C | acute myeloid leukemia | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring a FLT3 internal tandem duplication and expressing FLT3 Y842C demonstrated sensitivity to Rydapt (midostaurin) in culture (Blood 2009 114:3776). | detail... |
FLT3 exon 14 ins FLT3 Y842C | hematologic cancer | sensitive | FF-10101 | Preclinical - Cell culture | Actionable | In a preclinical study, FF-10101, as compared to Quizartinib, inhibited Flt3 autophosphorylation and cell proliferation of transformed 32Dcl3 murine myeloid cells expressing a human FLT3-ITD/Y842C compound mutation (PMID: 29187377). | 29187377 |
FLT3 exon 14 ins FLT3 Y842C | hematologic cancer | resistant | KW-2449 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 Y842C were resistant to treatment with KW-2449 in culture (PMID: 22858906). | 22858906 |
FLT3 exon 14 ins FLT3 Y842C | hematologic cancer | resistant | Quizartinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, cells expressing FLT3-ITD and FLT3 Y842C were resistant to treatment with Vanflyta (quizartinib) in culture and in a cell line xenograft model (PMID: 38231480). | 38231480 |
FLT3 exon 14 ins FLT3 Y842C | hematologic cancer | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed hematologic cells co-expressing FLT3 ITD and FLT3 Y842C were resistant to treatment with Vanflyta (quizartinib) in culture (PMID: 22858906). | 22858906 |
FLT3 exon 14 ins FLT3 Y842C | hematologic cancer | sensitive | LT-171-861 | Preclinical - Cell culture | Actionable | In a preclinical study, LT-171-861 inhibited cell viability and decreased FLT3 phosphorylation in transformed cells expressing a FLT3-ITD mutation and FLT3 Y842C in culture (PMID: 33391463). | 33391463 |
FLT3 exon 14 ins FLT3 Y842C | acute myeloid leukemia | sensitive | FF-10101 | Preclinical - Cell culture | Actionable | In a preclinical study, FF-10101 treatment inhibited growth of acute myeloid leukemia cells harboring FLT3-ITD and FLT3 Y842C in culture (PMID: 35395091). | 35395091 |
FLT3 exon 14 ins FLT3 Y842C | hematologic cancer | sensitive | Gilteritinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Xospata (gilteritinib) inhibited viability of cultured cells expressing FLT3-ITD with FLT3 Y842C and improved survival in a cell line xenograft model (PMID: 38231480). | 38231480 |
FLT3 exon 14 ins 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 ITD with FLT3 Y842C in culture (PMID: 32040554). | 32040554 |
FLT3 exon 14 ins FLT3 Y842C | acute myeloid leukemia | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) resulted in reduced cell viability in acute myeloid leukemia cells harboring FLT3 ITD with FLT3 Y842C in culture (PMID: 32040554). | 32040554 |
FLT3 exon 14 ins FLT3 Y842C | acute myeloid leukemia | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring FLT3 ITD with FLT3 Y842C were resistant to Vanflyta (quizartinib) in culture (PMID: 32040554). | 32040554 |
FLT3 exon 14 ins FLT3 Y842C | hematologic cancer | sensitive | Sitravatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Sitravatinib (MGCD516) inhibited proliferation of transformed hematologic cells expressing FLT3-ITD with FLT3 Y842C in culture, and resulted in an increased median survival compared to the vehicle-treated group (P<0.001) in a cell line xenograft model (PMID: 36691065). | 36691065 |
FLT3 exon 14 ins FLT3 Y842C | acute myeloid leukemia | sensitive | RMC-4550 | Preclinical - Cell culture | Actionable | In a preclinical study, RMC-4550 inhibited viability in an acute myeloid leukemia cell line harboring FLT3 ITD and expressing FLT3 Y842C in culture (PMID: 37992684). | 37992684 |
FLT3 exon 14 ins FLT3 Y842C | hematologic cancer | sensitive | Foretinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Foretinib (GSK1363089) inhibited viability of cultured cells expressing FLT3-ITD with FLT3 Y842C and improved survival in a cell line xenograft model (PMID: 38231480). | 38231480 |
FLT3 exon 14 ins FLT3 F691L FLT3 Y842C | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/Y842C mutation were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
FLT3 exon 14 ins FLT3 N676D FLT3 Y842C | leukemia | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines harboring FLT3 N676D and Y842C in addition to FLT3 internal tandem duplications (ITD) in culture (PMID: 26822154). | 26822154 |