en Adults Hematology & Oncology Adults Hematology & Oncology مقاله مروری Review Article <div style="text-align: justify;"><span style="line-height:2;"><span style="font-size:14px;"><span style="font-family:Times New Roman;">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&ndash;dependent and &ndash;independent resistance, and emerging strategies including combination therapy, degraders, and immunotherapeutic approaches. Real-world data and clinical trials demonstrate asciminib&rsquo;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.</span></span></span></div> Chronic Myeloid Leukemia, Asciminib, BCR-ABL1, Tyrosine Kinase Inhibitors, Drug Resistance 27 35 http://ijbc.ir/browse.php?a_code=A-10-1220-4&slc_lang=en&sid=1 Sanchita Srivastava 100319475328460012854 100319475328460012854 Yes Department of Biotechnology, Era’s Lucknow Medical College and Hospital Lucknow, India. Riya Nag 100319475328460012855 100319475328460012855 No Department of Biotechnology, Era’s Lucknow Medical College and Hospital Lucknow, India. Ale Eba 100319475328460012856 100319475328460012856 No Department of Biotechnology, Era’s Lucknow Medical College and Hospital Lucknow, India. Syed Tasleem Raza tasleem24@gmail.com 100319475328460012857 100319475328460012857 No Department of Biotechnology, Era’s Lucknow Medical College and Hospital Lucknow, India.