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Iranian Journal of Blood and Cancer، جلد ۱۷، شماره ۴، صفحات ۲۷-۳۵
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عنوان انگلیسی Mechanisms of Resistance in CML and the Emerging Role of Asciminib and Other Next-Generation Inhibitors
چکیده انگلیسی مقاله
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.
کلیدواژه‌های انگلیسی مقاله Chronic Myeloid Leukemia, Asciminib, BCR-ABL1, Tyrosine Kinase Inhibitors, Drug Resistance
نویسندگان مقاله | Sanchita Srivastava
Department of Biotechnology, Era’s Lucknow Medical College and Hospital Lucknow, India.


| Riya Nag
Department of Biotechnology, Era’s Lucknow Medical College and Hospital Lucknow, India.


| Ale Eba
Department of Biotechnology, Era’s Lucknow Medical College and Hospital Lucknow, India.


| Syed Tasleem Raza
Department of Biotechnology, Era’s Lucknow Medical College and Hospital Lucknow, India.
نشانی اینترنتی http://ijbc.ir/browse.php?a_code=A-10-1220-4&slc_lang=en&sid=1
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کد مقاله (doi)
زبان مقاله منتشر شده en
موضوعات مقاله منتشر شده Adults Hematology & Oncology
نوع مقاله منتشر شده مقاله مروری
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