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BCR::ABL1 T315I Gatekeeper-Mutation

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IDBIO-BCR-ABL1-T315I
ArtBiomarker
Aliase
ABL1 p.T315IBCR-ABL T315IBCR-ABL1 T315I Gatekeeper-MutationBCR::ABL1 T315I — мутація-gatekeeperT315I
Statusreviewed 2026-04-27 | pending_clinical_signoff
ErkrankungenNone declared
QuellenSRC-ASCEMBL-REA-2021 SRC-ELN-CML-2020 SRC-ELN-CML-2025 SRC-PACE-CORTES-2013

Biomarker-Fakten

Biomarker-Typgene_mutation
Angaben zur Mutation{"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"}
Messung
VerfahrenBCR::ABL1 Kinase-Domain Sanger-Sequenzierung ODER gezielte NGS bei TKI-Ausfall / suboptimale Reaktion
Einheitencategorical (positive | negative); VAF % when reported by NGS
SensitivitätsanforderungSanger-Empfindlichkeit ~10-20%; NGS für Low-VAF-Klone (~1-5%) empfohlen
Nachschlagewerk für die Aktionsfähigkeit‚Gen‘: ‚ABL1‘, ‚Variante‘:‚T315I‘}
Verwandte BiomarkerBIO-BCR-ABL1 BIO-BCR-ABL1-F317L BIO-BCR-ABL1-V299L BIO-BCR-ABL1-E255K

Anmerkungen

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.

Verwendet von

Biomarker