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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. | ||||||||||||
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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 | 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, Apr 2024). | Y |
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 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 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 Vanflyta (quizartinib) in culture (PMID: 23392356). | 23392356 |
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 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 Vanflyta (quizartinib) 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 | 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 | 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 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 Vanflyta (quizartinib) 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 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 Vanflyta (quizartinib) 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 | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and F691I were resistant to Vanflyta (quizartinib) 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 |