Lahmouad Meriem, Rachid Zahrae, Bellemrrabet Rawane, Zerrouk Jihane, Goh Khan Wen, Bouyahya Abdelhakim, Aboussalah Youssef
Biology and Health Laboratory, Department of Life Sciences, Faculty of sciences, University Ibn Tofail, B.P. 133, Kenitra 14000, Morocco.
Laboratory of Health Sciences and Technologies, Higher Institute of Health Sciences, Hassan First University of Settat, Settat 26000, Morocco.
Leuk Res Rep. 2025 Aug 5;24:100533. doi: 10.1016/j.lrr.2025.100533. eCollection 2025.
Chronic Myeloid Leukemia (CML) is characterized by aberrant BCR::ABL1 tyrosine kinase activity in hematopoietic stem cells. Although tyrosine kinase inhibitors (TKIs) have revolutionized CML treatment, resistance remains a major clinical challenge. This review provides a comprehensive overview of CML, including its epidemiology, pathophysiology, diagnosis, and treatment, as outlined in the latest WHO consensus classification. Current treatment paradigms and the prospects for treatment-free remission (TFR) are also explored. The primary focus is on elucidating the molecular mechanisms of TKI resistance, emphasizing both well-known pathways such as PI3K/AKT, MAPK, JAK/STAT, and alternative pathways including SRC/AKT. This review stands out by integrating recent discoveries regarding genetic mutations within the BCR::ABL1 gene, alongside other molecular alterations contributing to resistance. By synthesizing this knowledge, it aims to guide clinical practitioners, investigators, and translational researchers in developing innovative strategies to overcome resistance and improve patient outcomes in CML.
慢性髓系白血病（CML）的特征是造血干细胞中存在异常的BCR::ABL1酪氨酸激酶活性。尽管酪氨酸激酶抑制剂（TKIs）彻底改变了CML的治疗方式，但耐药性仍然是一个主要的临床挑战。本综述全面概述了CML，包括其流行病学、病理生理学、诊断和治疗，如最新的WHO共识分类中所述。还探讨了当前的治疗模式以及无治疗缓解（TFR）的前景。主要重点是阐明TKI耐药的分子机制，强调诸如PI3K/AKT、MAPK、JAK/STAT等知名途径以及包括SRC/AKT在内的替代途径。本综述通过整合有关BCR::ABL1基因内基因突变的最新发现以及其他导致耐药的分子改变而脱颖而出。通过综合这些知识，其旨在指导临床医生、研究人员和转化研究人员制定创新策略，以克服耐药性并改善CML患者的预后。
