BCR::ABL1 T315I gatekeeper mutation
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-BCR-ABL1-T315I |
|---|---|
| Type | Biomarker |
| Aliases | ABL1 p.T315IBCR-ABL T315IBCR-ABL1 T315I gatekeeper mutationBCR::ABL1 T315I — мутація-gatekeeperT315I |
| Status | reviewed 2026-04-27 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-ASCEMBL-REA-2021 SRC-ELN-CML-2020 SRC-ELN-CML-2025 SRC-PACE-CORTES-2013 |
Biomarker Facts
| Biomarker type | gene_mutation |
|---|---|
| Mutation details | {"exon": "6", "functional_impact": "pan-TKI resistance: imatinib, dasatinib, nilotinib, bosutinib all inactive; ponatinib and asciminib retain activity", "gene": "ABL1", "hgvs_protein": "p.T315I", "variant_type": "missense"} |
| Measurement | MethodBCR::ABL1 kinase-domain Sanger sequencing OR targeted NGS at TKI failure / suboptimal response Unitscategorical (positive | negative); VAF % when reported by NGS Sensitivity requirementSanger sensitivity ~10-20%; NGS recommended for low-VAF clones (~1-5%) |
| Actionability lookup | {"gene": "ABL1", "variant": "T315I"} |
| Related biomarkers | BIO-BCR-ABL1 BIO-BCR-ABL1-F317L BIO-BCR-ABL1-V299L BIO-BCR-ABL1-E255K |
Notes
Classical gatekeeper mutation analogous to EGFR T790M and ALK L1196M. T315 normally forms a hydrogen bond with imatinib; the T→I substitution introduces a bulky isoleucine side chain that sterically blocks all type-II ATP-competitive TKIs (imatinib, nilotinib, dasatinib, bosutinib). Ponatinib (PACE, Cortes 2013) was specifically designed to accommodate the I315 side chain via a triple-bond linker and remains active. Asciminib (ASCEMBL, Rea 2021) — an allosteric STAMP inhibitor binding the myristoyl pocket — also retains activity at higher doses (200 mg BID for T315I). Per ELN-2020 and ELN-2025, T315I screening is mandatory at TKI failure or suboptimal response; presence dictates ponatinib or asciminib choice over 2G-TKI. In Ph+ B-ALL, T315I emerges rapidly under non-ponatinib TKI pressure — ponatinib + chemo (or + blinatumomab) is preferred when detected.
Used By
Biomarker
BIO-BCR-ABL1- BCR::ABL1 fusion (Philadelphia chromosome)BIO-BCR-ABL1-E255K- BCR::ABL1 E255K nilotinib-resistance mutationBIO-BCR-ABL1-F317L- BCR::ABL1 F317L resistance mutationBIO-BCR-ABL1-V299L- BCR::ABL1 V299L dasatinib-resistance mutation