Meriem Lahmouad, Zahrae Rachid, Rawane Bellemrrabet, Jihane Zerrouk, Khan Wen Goh, Abdelhakim Bouyahya, Youssef Aboussalah
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. © 2025 The Author(s)
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; Flow Cytometry Laboratory, National Institute of Hygiene, Rabat, Morocco; Faculty of Data Science and Information Technology, INTI International University, Nilai, Malaysia; Faculty of Mathematics and Natural Sciences, Universitas Negeri Padang, Padang, Indonesia; Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, Mohammed V University in Rabat, 10106, Morocco
