FLT3 F691L mutation de gardien de gatekeeper de résistance au gilteritinib
Vue déterministe de l'entité source de la LJAM. L'autorité clinique demeure avec les ID de la source cités et l'état d'approbation de l ́examinateur.
| ID | BIO-FLT3-F691L |
|---|---|
| Type | Biomarqueur |
| Alias | FLT3 mutation de résistance du gardien de porte F691LFLT3 F691L — gatekeeper-мутація резистентності до гілтеритинібуPorte-porte FLT3FLT3 p.F691LFLT3-ITD F691L |
| État | reviewed 2026-04-27 | pending_clinical_signoff |
| Maladies | Aucune déclaration |
| Sources | SRC-ADMIRAL-PERL-2019 SRC-ELN-AML-2022 SRC-NCCN-AML-2025 |
Données biomarqueurs
| Type de biomarqueur | gene_mutation |
|---|---|
| Détails de la 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"} |
| Mesure | MéthodeTargeted NGS panel (FLT3-resistance panel) at FLT3-inhibitor failure / relapse; ddPCR for known F691L allele monitoring Unitéscategorical (positive | negative); VAF % when reported by NGS Exigence de sensibilitéEmergence sous-clonale commune — sensibilité à l'NGS ~1-2 % VAF préférée pour la détection précoce |
| Recherche de la faisabilité | {"générique": "FLT3", "variante":"F691L"} |
| Biomarqueurs connexes | BIO-FLT3-ITD BIO-FLT3-D835 BIO-NPM1 |
Notes
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.
Utilisé par
No reverse references found in the YAML corpus.