FLT3 tyrosine kinase domain (TKD) mutation
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-FLT3-D835 |
|---|---|
| Type | Biomarker |
| Aliases | FLT3 D835FLT3 I836FLT3-TKDFLT3-TKD (D835 / I836)Мутація тірозінкіназного домену FLT3 (TKD) |
| Status | reviewed 2026-04-27 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-ELN-AML-2022 SRC-NCCN-AML-2025 SRC-RATIFY-STONE-2017 |
Biomarker Facts
| Biomarker type | gene_mutation |
|---|---|
| Mutation details | {"exon": "20 (activation loop)", "functional_impact": "Constitutive FLT3 kinase activation via activation-loop conformational change", "gene": "FLT3", "gene_hugo_id": "HGNC:3765", "hotspots": ["D835Y", "D835V", "D835H", "D835E", "I836 deletion / substitution"], "variant_type": "missense"} |
| Measurement | MethodPCR + EcoRV restriction digest (classical) OR NGS panel Unitscategorical (positive/negative); VAF reported Sensitivity requirementRapid TAT preferred at AML diagnosis; type-II FLT3 inhibitors (quizartinib) less active against TKD vs type-I (gilteritinib, midostaurin) |
| Actionability lookup | {"gene": "FLT3", "variant": "D835Y"} |
| Related biomarkers | BIO-FLT3-ITD BIO-NPM1 |
Notes
~7–10% of AML; can co-occur with FLT3-ITD. Type-I FLT3 inhibitors (midostaurin, gilteritinib, crenolanib) inhibit both ITD and TKD; type-II (quizartinib, sorafenib) bind only inactive conformation and are less effective against D835. FLT3-TKD also acts as a resistance mechanism to type-II inhibitors during therapy. ELN-2022 classifies FLT3-TKD without ITD as intermediate-risk (revised down from adverse).
Used By
Actionability
BMA-FLT3-D835-AML- FLT3-D835 (TKD) in newly-diagnosed AML: midostaurin + 7+3 was studied in FLT3-mutant (ITD...BMA-FLT3-D835-AML-RR- FLT3-D835 in R/R AML: gilteritinib superior to salvage chemo (ADMIRAL, Perl 2019 — pre-sp...BMA-FLT3-F691L-AML- FLT3-F691L is a gatekeeper mutation arising under FLT3-TKI selective pressure (gilteritin...
Biomarker
BIO-FLT3-F691L- FLT3 F691L gilteritinib-resistance gatekeeper mutationBIO-FLT3-ITD- FLT3 internal tandem duplication (ITD)BIO-NPM1- NPM1 mutation (cytoplasmic NPM1)