Current outlook on drug resistance in chronic myeloid leukemia (CML) and potential therapeutic options.

Affiliation

Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada; Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB, Canada; Department of Biomedical Engineering, University of Alberta, Edmonton, AB, Canada. Electronic address: [Email]

Abstract

Chronic myeloid leukemia cells are armed with several resistance mechanisms that can make current drugs ineffective. A better understanding of resistance mechanisms is yielding new approaches to management of the disease. Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm the hallmark of which, the breakpoint cluster region-Abelson (BCR-ABL) oncogene, has been the target of tyrosine kinase inhibitors (TKIs), which have significantly improved the survival of patients with CML. However, because of an increase in TKI resistance, it is becoming imperative to identify resistance mechanisms so that drug therapies can be better prescribed and new agents developed. In this review, we discuss the various BCR-ABL-dependent and -independent mechanisms of resistance observed in CML, and the range of therapeutic solutions available to overcome such resistance and to ultimately improve the survival of patients with CML.