Management of chronic myeloid leukaemia: current treatment options, challenges, and future strategies
Small 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.
Other Information
Published in: Hematology
License: http://creativecommons.org/licenses/by/4.0/
See article on publisher's website: https://dx.doi.org/10.1080/16078454.2023.2196866
Funding
Open Access funding provided by the Qatar National Library.
History
Language
- English
Publisher
Taylor & FrancisPublication Year
- 2023
License statement
This Item is licensed under the Creative Commons Attribution 4.0 International License.Institution affiliated with
- Hamad Medical Corporation
- Women's Wellness and Research Center - HMC
- Qatar University
- Qatar University Health - QU
- College of Health Sciences - QU HEALTH
- Academic Health System - HMC
- Interim Translational Research Institute - HMC
- Hamad Bin Khalifa University
- College of Health and Life Sciences - HBKU