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Ref Type
PMID (27908881)
Authors Lee LY, Hernandez D, Rajkhowa T, Smith SC, Raman JR, Nguyen B, Small D, Levis M
Title Preclinical studies of gilteritinib, a next-generation FLT3 inhibitor.
Journal Vol Issue Date Pages Journal Short Title
Blood 129 2 2017 01 12 257-260 Blood
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 D835I missense unknown FLT3 D835I lies within the protein kinase domain activation loop of the Flt3 protein (PMID: 11290608). D835I has been demonstrated to promote secondary drug resistance in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 27908881), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Dec 2023). Y
TET2 C1396R missense unknown TET2 C1396R lies within the catalytic domain of the Tet2 protein (PMID: 24315485). C1396R has been identified in sequencing studies (PMID: 27908881), but has not been biochemically characterized and therefore, its effect on Tet2 protein function is unknown (PubMed, Dec 2022).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 exon 14 ins FLT3 F691L FLT3 D835I acute myeloid leukemia predicted - resistant Crenolanib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) with FLT3 F691L and FLT3 D835I demonstrated resistance to Crenolanib (CP-868596) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia sensitive Gilteritinib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated sensitivity to Xospata (gilteritinib) treatment in culture, resulting in reduced cell viability (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 F691L FLT3 D835I acute myeloid leukemia predicted - resistant Gilteritinib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) with FLT3 F691L and FLT3 D835I demonstrated resistance to Xospata (gilteritinib) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835I acute myeloid leukemia predicted - resistant Sorafenib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835I demonstrated resistance to Nexavar (sorafenib) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia resistant Sorafenib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated resistance to Nexavar (sorafenib) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835I acute myeloid leukemia predicted - resistant Quizartinib Case Reports/Case Series Actionable In a clinical case study, FLT3 D835I was identified as an acquired resistance mutation in a patient with acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD) whose disease progressed on Vanflyta (quizartinib) after an initial response (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia predicted - resistant Midostaurin Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated resistance to Rydapt (midostaurin) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 F691L FLT3 D835I acute myeloid leukemia predicted - resistant Quizartinib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) with FLT3 F691L and FLT3 D835I demonstrated resistance to Vanflyta (quizartinib) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835I acute myeloid leukemia predicted - sensitive Gilteritinib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835I demonstrated sensitivity to Xospata (gilteritinib) treatment in culture, resulting in reduced cell viability and inhibition of Flt3 phosphorylation (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia resistant Quizartinib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated resistance to Vanflyta (quizartinib) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 F691L FLT3 D835I acute myeloid leukemia predicted - resistant Crenolanib Case Reports/Case Series Actionable In a clinical case study, FLT3 F691L was identified as an acquired resistance mutation in a patient with acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835I whose disease progressed following Crenolanib (CP-868596) treatment (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 F691L FLT3 D835I acute myeloid leukemia predicted - resistant Midostaurin Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) with FLT3 F691L and FLT3 D835I demonstrated resistance to Rydapt (midostaurin) treatment in culture (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia conflicting Crenolanib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) and FLT3 D835Y demonstrated sensitivity to Crenolanib (CP-868596) treatment in culture, resulting in reduced cell viability (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia resistant Sorafenib Case Reports/Case Series Actionable In a clinical case study, FLT3 D835Y was identified as an acquired resistance mutation in a patient with acute myeloid leukemia harboring a FLT3 internal tandem duplication (ITD) whose disease progressed on Nexavar (sorafenib) after initial response (PMID: 27908881). 27908881
FLT3 exon 14 ins FLT3 F691L FLT3 D835I acute myeloid leukemia predicted - resistant Sorafenib Preclinical - Patient cell culture Actionable In a preclinical study, a patient-derived acute myeloid leukemia cell line harboring a FLT3 internal tandem duplication (ITD) with FLT3 F691L and FLT3 D835I demonstrated resistance to Nexavar (sorafenib) treatment in culture (PMID: 27908881). 27908881