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Ref Type

PMID

(23392356)

Authors

Albers C, Leischner H, Verbeek M, Yu C, Illert AL, Peschel C, von Bubnoff N, Duyster J

Title

The secondary FLT3-ITD F691L mutation induces resistance to AC220 in FLT3-ITD+ AML but retains in vitro sensitivity to PKC412 and Sunitinib.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Leukemia	27	6	2013 Jun	1416-8	Leukemia

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Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance
FLT3	F691I	missense	unknown	FLT3 F691I lies within the protein kinase domain of the Flt3 protein (PMID: 23430109). F691I has been demonstrated to promote secondary drug resistance in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 23392356, PMID: 22409268), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Apr 2025).	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 A848P	Advanced Solid Tumor	decreased response	Sorafenib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells over expressing FLT3 ITD and A848P demonstrated reduced sensitivity to Nexavar (sorafenib) in culture (PMID: 23392356).	23392356
FLT3 exon 14 ins FLT3 A848P	Advanced Solid Tumor	resistant	Sunitinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells over expressing FLT3 ITD and A848P were resistant to Sutent (sunitinib) in culture (PMID: 23392356).	23392356
FLT3 exon 14 ins FLT3 A848P	Advanced Solid Tumor	decreased response	Quizartinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells over expressing FLT3 ITD and A848P demonstrated reduced sensitivity to Vanflyta (quizartinib) in culture (PMID: 23392356).	23392356
FLT3 exon 14 ins FLT3 F691I	Advanced Solid Tumor	decreased response	Sunitinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells over expressing FLT3 ITD and F691I demonstrated reduced response to Sutent (sunitinib) in culture (PMID: 23392356).	23392356
FLT3 exon 14 ins FLT3 F691I	Advanced Solid Tumor	resistant	Midostaurin	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells over expressing FLT3 ITD and F691I were resistant to Rydapt (midostaurin) in culture (PMID: 23392356).	23392356
FLT3 exon 14 ins FLT3 F691I	Advanced Solid Tumor	resistant	Sorafenib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells over expressing FLT3 ITD and F691I were resistant to Nexavar (sorafenib) in culture (PMID: 23392356).	23392356
FLT3 exon 14 ins FLT3 F691I	Advanced Solid Tumor	resistant	Quizartinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells over expressing FLT3 ITD and F691I were resistant to Vanflyta (quizartinib) in culture (PMID: 23392356).	23392356
FLT3 exon 14 ins FLT3 F691L	Advanced Solid Tumor	resistant	Sorafenib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells over expressing FLT3 ITD and F691L were resistant to Nexavar (sorafenib) in culture (PMID: 23392356).	23392356
FLT3 exon 14 ins FLT3 F691L	Advanced Solid Tumor	resistant	Quizartinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells over expressing FLT3 ITD and F691L were resistant to Vanflyta (quizartinib) in culture (PMID: 23392356).	23392356
FLT3 exon 14 ins FLT3 N676D	Advanced Solid Tumor	decreased response	Quizartinib	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells over expressing FLT3 ITD and N676D demonstrated reduced sensitivity to Vanflyta (quizartinib) in culture (PMID: 23392356).	23392356
FLT3 exon 14 ins FLT3 N676D	Advanced Solid Tumor	resistant	Midostaurin	Preclinical - Cell culture	Actionable	In a preclinical study, transformed cells over expressing FLT3 ITD and N676D were resistant to Rydapt (midostaurin) in culture (PMID: 23392356).	23392356
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

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