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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

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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

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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