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BCR::ABL1 E255K nilotinib-resistance mutation

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

IDBIO-BCR-ABL1-E255K
TypeBiomarker
Aliases
ABL1 p.E255KBCR-ABL E255KBCR-ABL1 E255K resistance mutationBCR::ABL1 E255K — мутація резистентності до нілотинібуP-loop mutation
Statusreviewed 2026-04-27 | pending_clinical_signoff
DiseasesNone declared
SourcesSRC-ELN-CML-2020 SRC-ELN-CML-2025 SRC-ESMO-CML-2017

Biomarker Facts

Biomarker typegene_mutation
Mutation details{"exon": "4", "functional_impact": "partial nilotinib resistance and reduced imatinib sensitivity; dasatinib, bosutinib, ponatinib retain activity", "gene": "ABL1", "hgvs_protein": "p.E255K", "variant_type": "missense"}
Measurement
MethodBCR::ABL1 kinase-domain Sanger sequencing OR targeted NGS at TKI failure
Unitscategorical (positive | negative); VAF % when NGS
Actionability lookup{"gene": "ABL1", "variant": "E255K"}
Related biomarkersBIO-BCR-ABL1 BIO-BCR-ABL1-T315I BIO-BCR-ABL1-V299L

Notes

Classical P-loop mutation of ABL1. Reduces nilotinib sensitivity (IC50 ~5-7x baseline) and imatinib sensitivity (IC50 ~10-20x); associated with adverse prognosis on imatinib. Dasatinib, bosutinib, ponatinib retain in-vitro activity. Per ELN-2020 / ELN-2025: detection on nilotinib or imatinib failure → switch to dasatinib (preferred 2G-TKI option) or ponatinib. P-loop mutations as a class (E255K, Y253H, G250E) generally favor dasatinib-based salvage; T315I excluded per separate biomarker.

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Biomarker