FLT3 F691L gilteritinib-resistance gatekeeper mutation
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-FLT3-F691L |
|---|---|
| Type | Biomarker |
| Aliases | FLT3 F691L gatekeeper resistance mutationFLT3 F691L — gatekeeper-мутація резистентності до гілтеритинібуFLT3 gatekeeperFLT3 p.F691LFLT3-ITD F691L |
| Status | reviewed 2026-04-27 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-ADMIRAL-PERL-2019 SRC-ELN-AML-2022 SRC-NCCN-AML-2025 |
Biomarker Facts
| Biomarker type | gene_mutation |
|---|---|
| Mutation details | {"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"} |
| Measurement | MethodTargeted NGS panel (FLT3-resistance panel) at FLT3-inhibitor failure / relapse; ddPCR for known F691L allele monitoring Unitscategorical (positive | negative); VAF % when reported by NGS Sensitivity requirementSubclonal emergence common — NGS sensitivity ~1-2% VAF preferred for early detection |
| Actionability lookup | {"gene": "FLT3", "variant": "F691L"} |
| Related biomarkers | 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.
Used By
No reverse references found in the YAML corpus.