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Management of chronic myeloid leukaemia: current treatment options, challenges, and future strategies
- Source :
- Hematology, Vol 28, Iss 1 (2023)
- Publication Year :
- 2023
- Publisher :
- Taylor & Francis Group, 2023.
-
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.
Details
- Language :
- English
- ISSN :
- 16078454 and 17564964
- Volume :
- 28
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Hematology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.76b7560e6e04ca0aa7a65b175649647
- Document Type :
- article
- Full Text :
- https://doi.org/10.1080/16078454.2023.2196866