FLT3 F691L Gilteritinib-Widerstands-Gatekeeper-Mutation
Deterministische Ansicht der Quelle YAML Entität. Klinische Autorität bleibt mit den zitierten Quell-IDs und Rezensenten Sign-off Zustand.
| ID | BIO-FLT3-F691L |
|---|---|
| Art | Biomarker |
| Aliase | FLT3 F691L Gatekeeper ResistenzmutationFLT3 F691L — gatekeeper-мутація резистентності до гілтеритинібуFLT3-TorhüterFLT3 p.F691LFLT3-ITD F691L |
| Status | reviewed 2026-04-27 | pending_clinical_signoff |
| Erkrankungen | None declared |
| Quellen | SRC-ADMIRAL-PERL-2019 SRC-ELN-AML-2022 SRC-NCCN-AML-2025 |
Biomarker-Fakten
| Biomarker-Typ | gene_mutation |
|---|---|
| Angaben zur Mutation | {"exon": "14", "functional_impact": "acquired gatekeeper resistance to FLT3 inhibitors (gilteritinib, quizartinib, midostaurin); typically emerges on top of pre-existing FLT3-ITD", "gene": "FLT3", "gene_hugo_id": "HGNC:3765", "hgvs_protein": "p.F691L", "variant_type": "missense"} |
| Messung | VerfahrenZielgerichtetes NGS-Panel (FLT3-Resistenzpanel) bei FLT3-Hemmerversagen / Rückfall; ddPCR für bekannte F691L-Allelüberwachung Einheitencategorical (positive | negative); VAF % when reported by NGS SensitivitätsanforderungSubklonale Entstehung häufig — NGS-Empfindlichkeit ~1-2% VAF bevorzugt für die Früherkennung |
| Nachschlagewerk für die Aktionsfähigkeit | {"gene": "FLT3", "Variante":"F691L"} |
| Verwandte Biomarker | BIO-FLT3-ITD BIO-FLT3-D835 BIO-NPM1 |
Anmerkungen
FLT3 gatekeeper mutation analogous to BCR::ABL1 T315I, EGFR T790M, and ALK L1196M. Almost always emerges on top of pre-existing FLT3-ITD (rarely de novo). Most clinically relevant as acquired resistance to gilteritinib in relapsed/refractory FLT3-mut AML — the dominant on-target mechanism per ADMIRAL (Perl 2019, NEJM) post-progression series and several real-world cohorts. F691L also reduces quizartinib activity (originally a type-II FLT3 inhibitor with even narrower resistance profile) and midostaurin. No commercially available FLT3 inhibitor reliably overcomes F691L; clinical trials of next-generation FLT3 inhibitors (FF-10101, MAX-40279) and combination strategies (FLT3i + venetoclax, FLT3i + hypomethylator) are the current investigational options. Detection at gilteritinib relapse → route to alloSCT (if not already done), trial enrollment, or venetoclax-based salvage.
Verwendet von
Keine Rückverweise im YAML-Korpus gefunden.