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December 8, 2025BloodOpen Access

ASXL1 and NOTCH1 mutations independently predict TKI treatment failure in chronic myeloid leukemia

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Authors

TZTian ZengXYXiudi Yang

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Overview

Findings demonstrate ASXL1 and NOTCH1 mutations are significant predictors of TKI treatment failure in chronic myeloid leukemia patients, implying new genomic targets for resistance.

Key Points

  • The study aims to investigate the impact of ASXL1 and NOTCH1 mutations on treatment outcomes in chronic myeloid leukemia.
  • Retrospective analysis of 94 CML patients who underwent NGS with an 84-gene myeloid panel.
  • Assessment of TKI treatment failure based on ELN 2020 guidelines and mutational burden.
  • Utilization of univariable and multivariable logistic regression for data analysis.
  • ASXL1 and NOTCH1 mutations significantly associated with TKI failure in analysis.
  • Patients in TKI-failure group had lower hemoglobin and platelet counts compared to non-failures.
  • Higher mutation burden correlated with older age, first-generation TKI use, and lack of 12-month major molecular response.

Cite This Study

Zeng et al. (2025) studied this question.

synapsesocial.com/papers/69362f764fa91c937236e427https://doi.org/10.1182/blood-2025-5551
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Genetic evolution in CML patients from diagnosis to TKI failure: An analysis of 121 paired diagnosis and treatment failure samples2025
  2. 2Impact of Somatic Mutations on Treatment Response and Resistance in Chronic Myeloid Leukemia2026
  3. 3Mutations in myeloid transcription factors and activated signaling genes predict chronic myeloid leukemia outcomes2024 · 16 citations
  4. 4Somatic mutations at diagnosis in patients with chronic Phase CML receiving frontline imatinib are associated with a higher rate of treatment failure: First analysis from the international CML foundation (iCMLf) genomics alliance on the harmony platform2025 · 1 citations
  5. 5Prognostic impact of ASXL1 somatic mutation on patients with chronic myeloid leukemia: A systemic review and meta-analysis.2026