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BCR-ABL1 T315I is the gatekeeper mutation conferring pan-resistance to imatinib, dasatini...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

IDBMA-BCR-ABL1-T315I-CML
TypeActionability
Statusreviewed 2026-04-27 | pending_clinical_signoff | actionability review required
DiseasesDIS-CML
SourcesSRC-CIVIC SRC-ELN-CML-2025 SRC-PACE-CORTES-2013

Actionability Facts

BiomarkerBIO-BCR-ABL1
VariantT315I (gatekeeper resistance)
DiseaseDIS-CML
ESCAT tierIA
Recommended combinationsponatinib monotherapy, asciminib monotherapy (200 mg BID for T315I)
Contraindicated monotherapyimatinib (resistant), dasatinib (resistant), nilotinib (resistant), bosutinib (resistant)
Evidence summaryBCR-ABL1 T315I is the gatekeeper mutation conferring pan-resistance to imatinib, dasatinib, nilotinib, and bosutinib. Ponatinib (PACE, Cortes 2013) is approved for T315I+ CML. Asciminib (allosteric STAMP inhibitor) at higher dose (200 mg BID) also has T315I activity per ASCEMBL extension and dedicated cohorts. Allo-HCT remains a salvage option in eligible patients.

Notes

OncoKB R1. ABL1 kinase domain mutation testing mandatory at TKI failure or warning per ELN. Ponatinib cardiovascular risk requires dose-optimization (OPTIC trial, Cortes 2021).

Used By

No reverse references found in the YAML corpus.