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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. | ||||||||||||
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Abstract Text |
Molecular Profile | Treatment Approach |
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Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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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, Nov 2024). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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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 | 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 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 | 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 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 | 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 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 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 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 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 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 |
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 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 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 |