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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 Leukemia
Vol 27
Issue 6
Date 2013 Jun
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 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, Mar 2020). Y
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 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 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 Quizartinib (AC220) 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 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 Quizartinib (AC220) 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 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 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 Quizartinib (AC220) 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 Quizartinib (AC220) 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 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 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 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 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 Quizartinib (AC220) in culture (PMID: 23392356). 23392356