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Ref Type
PMID (33780043)
Authors Joshi SK, Sharzehi S, Pittsenbarger J, Bottomly D, Tognon CE, McWeeney SK, Druker BJ, Traer E
Title A noncanonical FLT3 gatekeeper mutation disrupts gilteritinib binding and confers resistance.
Journal Vol Issue Date Pages Journal Short Title
American journal of hematology 96 7 2021 07 01 E226-E229 Am J Hematol
URL
Abstract Text

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
FLT3 N701K missense gain of function - predicted FLT3 N701K lies within the protein kinase domain of the Flt3 protein (UniProt.org). N701K results in transformation activity and has been associated with resistance to some FLT3 inhibitors in the context of FLT3-ITD in cultured cells (PMID: 33780043), and therefore, is predicted to lead to a gain of Flt3 protein function. Y
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 exon 14 ins FLT3 N701K hematologic cancer resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 N701K demonstrated resistance to treatment with Rydapt (midostaurin) in culture (PMID: 33780043). 33780043
FLT3 exon 14 ins FLT3 N701K hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 N701K in culture (PMID: 33780043). 33780043
FLT3 N701K hematologic cancer resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3 N701K were resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33780043). 33780043
FLT3 exon 14 ins FLT3 N701K hematologic cancer resistant Crenolanib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 N701K demonstrated resistance to treatment with Crenolanib (CP-868596) in culture (PMID: 33780043). 33780043
FLT3 exon 14 ins FLT3 F691L hematologic cancer predicted - resistant Crenolanib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 F691L demonstrated resistance to treatment with Crenolanib in culture (PMID: 33780043). 33780043
FLT3 exon 14 ins FLT3 F691L hematologic cancer resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 F691L demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33780043). 33780043
FLT3 exon 14 ins FLT3 F691L hematologic cancer resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 F691L demonstrated resistance to treatment with Vanflyta (quizartinib) in culture (PMID: 33780043). 33780043
FLT3 exon 14 ins FLT3 N701K hematologic cancer resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 N701K demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33780043). 33780043
FLT3 exon 14 ins FLT3 F691L hematologic cancer resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 F691L demonstrated resistance to treatment with Rydapt (midostaurin) in culture (PMID: 33780043). 33780043