NOTCH1 activating mutations occur in >50% of T-ALL (HD and PEST domains). Gamma-secretase...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-NOTCH1-ACTIVATING-T-ALL |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-T-ALL |
| Sources | SRC-BLAST-GOKBUGET-2018 SRC-CALGB-10403-STOCK-2019 SRC-CIVIC |
Actionability Facts
| Biomarker | BIO-NOTCH1-MUTATION |
|---|---|
| Variant | activating (HD or PEST domain) |
| Disease | DIS-T-ALL |
| ESCAT tier | IIIA |
| Recommended combinations | per CALGB-10403 / GMALL / BFM-inspired regimen (1L), nelarabine (R/R T-ALL), venetoclax + navitoclax (early-phase trials) |
| Evidence summary | NOTCH1 activating mutations occur in >50% of T-ALL (HD and PEST domains). Gamma-secretase inhibitors (GSI) showed activity but were limited by GI toxicity. No GSI is FDA-approved in T-ALL. Standard 1L remains pediatric-inspired regimens (BFM, CALGB-10403). MRD-directed nelarabine/PEG-asparaginase per protocol. |
Notes
ESCAT IIIA. OncoKB Level 4. Favorable prognostic in some pediatric-T-ALL series when isolated; adverse with PTEN co-loss.
Used By
No reverse references found in the YAML corpus.