FLT3-F691L is a gatekeeper mutation arising under FLT3-TKI selective pressure (gilteritin...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-FLT3-F691L-AML |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-AML |
| Sources | SRC-ADMIRAL-PERL-2019 SRC-CIVIC SRC-ELN-AML-2022 |
Actionability Facts
| Biomarker | BIO-FLT3-D835 |
|---|---|
| Variant | F691L gatekeeper resistance mutation (post-FLT3i) |
| Disease | DIS-AML |
| ESCAT tier | IIA |
| Recommended combinations | salvage chemo + allo-SCT (preferred when fit), clinical trial (next-gen FLT3i, crenolanib, FF-10101), venetoclax + azacitidine (off-label salvage) |
| Contraindicated monotherapy | gilteritinib (cross-resistance F691L), quizartinib (cross-resistance F691L) |
| Evidence summary | FLT3-F691L is a gatekeeper mutation arising under FLT3-TKI selective pressure (gilteritinib, quizartinib). Confers cross-resistance to most current FLT3i. Crenolanib (investigational type-I) and next-gen FLT3i retain partial activity. No approved targeted option — clinical trial enrollment or salvage chemo + allo-SCT. |
Notes
ESCAT IIA (resistance biomarker — guides what NOT to use). OncoKB Level R1. Cell intentionally uses BIO-FLT3-D835 as biomarker_id because F691L is a TKD/kinase-domain mutation captured under the FLT3-D835 / TKD entity per the cherry-picked BIO file (no separate F691L biomarker). variant_qualifier disambiguates. Clinical use: trigger ctDNA / BM rebiopsy at gilteritinib failure to detect F691L vs D835 emergence.
Used By
Actionability
BMA-FLT3-ITD-AML-RR- FLT3-ITD in relapsed/refractory AML: gilteritinib monotherapy superior to salvage chemo (...