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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

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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

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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 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	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
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 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 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	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 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 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 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

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