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Gene FLT3
Variant Y842H
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions FLT3 Y842H lies within the protein kinase domain of the Flt3 protein (UniProt.org). Y842H results in increased phosphorylation of Flt3, activation of Stat5 and Mapk, and transformation of cultured cells (PMID: 14604974), and is associated with acquired resistance in the context of FLT3-ITD (PMID: 25847190, PMID: 22504184, PMID: 29187377).
Associated Drug Resistance Y
Category Variants Paths

FLT3 mutant FLT3 exon20 FLT3 Y842H

FLT3 mutant FLT3 act mut FLT3 Y842H

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Transcript NM_004119.3
gDNA chr13:g.28018484A>G
cDNA c.2524T>C
Protein p.Y842H
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004119 chr13:g.28018484A>G c.2524T>C p.Y842H RefSeq GRCh38/hg38
NM_004119.3 chr13:g.28018484A>G c.2524T>C p.Y842H RefSeq GRCh38/hg38
NM_004119.2 chr13:g.28018484A>G c.2524T>C p.Y842H 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 Y842H Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD with FLT3 Y842H were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 Y842H Advanced Solid Tumor decreased response Sorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and Y842H demonstrated reduced sensitivity to Nexavar (sorafenib) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 Y842H Advanced Solid Tumor decreased response Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing FLT3 ITD and Y842H demonstrated reduced sensitivity to Vanflyta (quizartinib) in culture (PMID: 23392356). 23392356
FLT3 exon 14 ins FLT3 Y842H 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 Y842H in culture (PMID: 27158668). 27158668
FLT3 exon 14 ins FLT3 Y842H 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/Y842H compound mutation (PMID: 29187377). 29187377
FLT3 exon 14 ins FLT3 Y842H hematologic cancer sensitive HQP1351 Preclinical - Cell culture Actionable In a preclinical study, GZD824 (HQP1351) inhibited growth of transformed cells expressing FLT3-ITD and FLT3 Y842H in culture (PMID: 32247263). 32247263
FLT3 exon 14 ins FLT3 Y842H 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 Y842H in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 Y842H hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited proliferation of transformed cells expressing FLT3-ITD and FLT3 Y842H in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 Y842H 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 Y842H in culture (PMID: 32040554). 32040554
FLT3 exon 14 ins FLT3 Y842H 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 Y842H in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 Y842H hematologic cancer resistant Sorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 Y842H demonstrated resistance to Nexavar (sorafenib) in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 Y842H hematologic cancer resistant Pacritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 Y842H demonstrated resistance to Vonjo (pacritinib) in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 Y842H hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 Y842H were sensitive to Rydapt (midostaurin) treatment in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 Y842H hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 Y842H were sensitive to Crenolanib (CP-868596) treatment in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 F691L FLT3 Y842H Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/Y842H mutation were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 F691L FLT3 Y842H hematologic cancer resistant Pacritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD, FLT3 F691L, and FLT3 Y842H demonstrated resistance to Vonjo (pacritinib) in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 F691L FLT3 Y842H hematologic cancer resistant Sorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD, FLT3 F691L, and FLT3 Y842H demonstrated resistance to Nexavar (sorafenib) in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 F691L FLT3 Y842H hematologic cancer resistant Crenolanib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD, FLT3 F691L, and FLT3 Y842H demonstrated resistance to Crenolanib (CP-868596) in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 F691L FLT3 Y842H hematologic cancer resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD, FLT3 F691L, and FLT3 Y842H demonstrated resistance to Xospata (gilteritinib) in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 F691L FLT3 Y842H hematologic cancer resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD, FLT3 F691L, and FLT3 Y842H demonstrated resistance to Vanflyta (quizartinib) in culture (PMID: 34768286). 34768286