%0 Review
%T Management of chronic myeloid leukaemia: current treatment options, challenges, and future strategies.
%A Younes S
%A Ismail MA
%A Al-Jurf R
%A Ziyada A
%A Nasrallah GK
%A Abdulrouf PV
%A Nagy M
%A Zayed H
%A Farrell T
%A Sorio C
%A Morsi H
%A Qoronfleh MW
%A Al-Dewik NI
%J Hematology
%V 28
%N 1
%D 2023 Dec
%M 37078896
%F 2.264
%R 10.1080/16078454.2023.2196866
%X 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.