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Management of chronic myeloid leukaemia: current treatment options, challenges, and future strategies

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submitted on 2024-02-08, 10:19 and posted on 2024-02-11, 13:03 authored by Salma Younes, Mohamed A. Ismail, Rana Al-Jurf, Ayah Ziyada, Gheyath K. Nasrallah, Palli Valapila Abdulrouf, Mohamed Nagy, Hatem Zayed, Thomas Farrell, Claudio Sorio, Hisham Morsi, M. Walid Qoronfleh, Nader I. Al-Dewik

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 & Francis

Publication 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