Mechanisms of Resistance in CML and the Emerging Role of Asciminib and Other Next-Generation Inhibitors

Srivastava, Sanchita; Nag, Riya; Eba, Ale; Raza, Syed Tasleem

Volume 17, Issue 4 (December-2025 2025) Iranian Journal of Blood and Cancer 2025, 17(4): 27-35 | Back to browse issues page

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Srivastava S, Nag R, Eba A, Raza S T. Mechanisms of Resistance in CML and the Emerging Role of Asciminib and Other Next-Generation Inhibitors. Iranian Journal of Blood and Cancer 2025; 17 (4) :27-35
URL: http://ijbc.ir/article-1-1830-en.html

Mechanisms of Resistance in CML and the Emerging Role of Asciminib and Other Next-Generation Inhibitors

Sanchita Srivastava ^*¹

, Riya Nag¹

, Ale Eba¹

, Syed Tasleem Raza¹

1- Department of Biotechnology, Era’s Lucknow Medical College and Hospital Lucknow, India.

Abstract: (17 Views)

Chronic myeloid leukemia (CML) is a myeloproliferative disorder driven by the BCR-ABL1 fusion gene that confers constitutive tyrosine kinase activity. Although tyrosine kinase inhibitors (TKIs) have revolutionized CML therapy, resistance remains a major clinical challenge, primarily due to kinase domain mutations, leukemic stem cell persistence, and compensatory signalling pathways. Asciminib, a novel allosteric STAMP inhibitor targeting the ABL myristoyl pocket, introduces a distinct mechanism to overcome resistance associated with ATP-site mutations such as T315I. This review highlights the molecular basis of TKI resistance, mechanisms of BCR-ABL1–dependent and –independent resistance, and emerging strategies including combination therapy, degraders, and immunotherapeutic approaches. Real-world data and clinical trials demonstrate asciminib’s efficacy and favorable safety in multi-resistant CML. The future of CML management lies in precision-driven multimodal therapy aimed at eradicating leukemic stem cells and achieving treatment-free remission.

Keywords: Chronic Myeloid Leukemia, Asciminib, BCR-ABL1, Tyrosine Kinase Inhibitors, Drug Resistance

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: Review Article | Subject: Adults Hematology & Oncology
Received: 2025/11/7 | Accepted: 2025/12/17 | Published: 2025/12/30

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