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Ref Type

PMID

(26012842)

Authors

Chatain N, Perera RC, Rossetti G, Rossa J, Carloni P, Schemionek M, Haferlach T, Brümmendorf TH, Schnittger S, Koschmieder S

Title

Rare FLT3 deletion mutants may provide additional treatment options to patients with AML: an approach to individualized medicine.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Leukemia	29	12	2015 Dec	2434-8	Leukemia

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Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance
FLT3	F590_D593delinsLY	indel	gain of function	FLT3 F590_D593delinsLY results in a deletion of four amino acids in the juxtamembrane domain of the Flt3 protein from amino acids 590 to 593, combined with the insertion of a leucine (L) and a tyrosine (Y) at the same site (PMID: 11756186). F590_D593delinsLY confers a gain of function to Flt3 as demonstrated by increased Flt3 downstream signaling, decreased apoptosis, weak clonogenic growth, and cytokine-independent growth in cultured cells (PMID: 26012842).
FLT3	E598_Y599del	deletion	gain of function	FLT3 E598_Y599del results in the deletion of two amino acids in the juxtamembrane domain of the Flt3 protein from amino acid 598 to 599 (PMID: 11756186). E598_Y599del confers a gain of function to Flt3 as demonstrated by increased Flt3 downstream signaling, decreased apoptosis, clonogenic growth, and cytokine-independent growth in cultured cells (PMID: 26012842).

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Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
FLT3 E598_Y599del	hematologic cancer	sensitive	Midostaurin	Preclinical - Cell culture	Actionable	In a preclinical study, Rydapt (midostaurin) inhibited Flt3 and Stat5 phosphorylation and viability in cells expressing FLT3 E598_Y599del in culture (PMID: 26012842).	26012842
FLT3 E598_Y599del	hematologic cancer	sensitive	Quizartinib	Preclinical - Cell culture	Actionable	In a preclinical study, Vanflyta (quizartinib) inhibited Flt3 and Stat5 phosphorylation and viability in cells expressing FLT3 E598_Y599del in culture (PMID: 26012842).	26012842
FLT3 F590_D593delinsLY	hematologic cancer	sensitive	Midostaurin	Preclinical - Cell culture	Actionable	In a preclinical study, Rydapt (midostaurin) inhibited Flt3 and Stat5 phosphorylation and viability in cells expressing FLT3 F590_D593delinsLY in culture (PMID: 26012842).	26012842
FLT3 F590_D593delinsLY	hematologic cancer	sensitive	Quizartinib	Preclinical - Cell culture	Actionable	In a preclinical study, Vanflyta (quizartinib) inhibited Flt3 and Stat5 phosphorylation and viability in cells expressing FLT3 F590_D593delinsLY in culture (PMID: 26012842).	26012842

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