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Updated: Aug 2, 2025
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
Published on: June 6, 2025
Management of chronic myeloid leukaemia: current treatment options, challenges, and future strategies
Salma Younes1,2, Mohamed A Ismail1,3,4, Rana Al-Jurf2
1Department of Research, Women's Wellness and Research Center, Hamad Medical Corporation, Doha, Qatar.
Abstract:
ABSTRACTSmall molecule therapy is a critical component of targeted anticancer treatment, with tyrosine kinase inhibitors (TKIs) being the first compounds to treat the clonal Chronic Myelogenous Leukaemia (CML) translocation t (9;22) (q34; q11) effectively since 2001. TKIs, such as imatinib, have improved the 10-year survival rate of CML patients to 80%. They bind the BCR::ABL1 kinase and inhibit downstream signaling pathways. However, therapy failure may be seen in 20-25% of CML patients due to intolerance or inadequacy related to BCR::ABL1 dependent or independent mechanisms. This review aimed to summarize current treatment options involving TKIs, resistance mechanisms and the prospective approaches to overcome TKI resistance. We highlight BCR::ABL1-dependent mechanisms of TKI resistance by reviewing clinically-documented BCR::ABL1 mutations and their consequences for TKI binding. In addition, we summarize BCR::ABL1 independent pathways, including the relevance of drug efflux, dysregulation of microRNA, and the involvement of alternative signaling pathways. We also discuss future approaches, such as gene-editing techniques in the context of CML, as potential therapeutic strategies.
Insights
Tyrosine kinase inhibitors (TKIs) have improved survival for Chronic Myelogenous Leukaemia (CML) patients, but resistance remains a challenge. This review explores TKI resistance mechanisms and future strategies for overcoming them.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Small molecule therapy, particularly tyrosine kinase inhibitors (TKIs), revolutionized Chronic Myelogenous Leukaemia (CML) treatment.
- TKIs targeting the BCR::ABL1 kinase have significantly improved patient survival rates since 2001.
- However, 20-25% of CML patients experience treatment failure due to resistance.
Conclusions:
- Understanding TKI resistance mechanisms is crucial for improving CML patient outcomes.
- Targeting both BCR::ABL1-dependent and independent pathways is necessary.
- Novel therapeutic approaches, including gene editing, offer potential solutions for resistant CML.
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