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Ref Type
PMID (20520641)
Authors von Bubnoff N, Rummelt C, Menzel H, Sigl M, Peschel C, Duyster J
Title Identification of a secondary FLT3/A848P mutation in a patient with FLT3-ITD-positive blast phase CMML and response to sunitinib and sorafenib.
Journal Vol Issue Date Pages Journal Short Title
Leukemia 24 8 2010 Aug 1523-5 Leukemia
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 A848P missense gain of function - predicted FLT3 A848P lies within the protein kinase domain of the Flt3 protein (UniProt.org). A848P results in growth factor independent cell proliferation, Flt3 phosphorylation, and Erk activation in culture (Blood; 2009, 114;22, Abstract #3982), and has been demonstrated to confer resistance to FLT3 inhibitors in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations in culture (PMID: 20520641), 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 A848P chronic myelomonocytic leukemia predicted - resistant Sorafenib + Sunitinib Case Reports/Case Series Actionable In a clinical case study, FLT3 A848P was identified after progression on the alternating treatment of Nexvar (sorafenib) and Sutent (sunitinib) in a patient with chronic myelomoncytic leukemia harboring a FLT3-ITD mutation (PMID: 20520641). 20520641
FLT3 exon 14 ins FLT3 A848P hematologic cancer resistant Sorafenib Preclinical - Cell culture Actionable In a preclinical study, cells expressing FLT3-ITD with FLT3 A848P were resistant to Nexavar (sorafenib) in culture (PMID: 20520641). 20520641
FLT3 exon 14 ins FLT3 A848P hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) treatment inhibited growth of cells expressing FLT3-ITD with FLT3 A848P in culture (PMID: 20520641). 20520641
FLT3 exon 14 ins FLT3 A848P hematologic cancer resistant Sunitinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing FLT3-ITD with FLT3 A848P were resistant to Sutent (sunitinib) in culture (PMID: 20520641). 20520641