Developing therapeutic approaches for chronic myeloid leukemia: a review

Abstract

Modern clinical therapy of chronic myeloid leukemia (CML) with TKIs is highly efficacious in most CML patients, while it is not remedial and generally confined due to intolerance or resistance. CML is currently considered a severe disease. Interestingly, stem cell transplantation in the past decade was an attractive clinical therapeutic option in CML patients, but it is not successful due to independently more death rates in older patients. So, the targeting of BCR::ABL oncoprotein is extensively used to enhance the reduction in a higher percentage of CML patients by tyrosine kinase inhibitors (TKIs). However, resistance or intolerance responses to these inhibitors are responsible for future deterioration and further development of disease. At this point, the clinical treatment of CML is a major challenge, and the lack of molecular responses to TKIs are not succeeded with chemotherapy alone. So, the considerable efficacious clinical necessities remain unmet. Therefore, continuous efforts are needed to explore new potential treatment strategies with an increasing understanding of CML biology. Therefore, this review deals with the investigation of TKI treatment with interferon, chemotherapy (Hydroxyurea, Homoharringtonine, Omacetaxine, Cytarabine), and several other new TKIs under beneficial clinical trials. Additionally, the approaches towards TKIs-resistant or intolerant CML cells where the respective signaling pathway gets up-regulated are also targeted with its inhibitor. This review presents evidence that new TKIs under clinical and pre-clinical trials may improve the chemotherapy of CML.

Keywords: ATP binding cassette (ABC); Chronic myeloid leukemia (CML); Multidrug resistance (MDR); Philadelphia chromosome (Ph); Tyrosine kinase inhibitors (TKIs).