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Multidrug resistance in chronic myeloid leukemia

Chronic myeloid leukemia (CML) is characterized by the accumulation of Philadelphia chromosome-positive (Ph+) myeloid cells. Ph+ cells occur via a reciprocal translocation between the long arms of chromosomes 9 and 22 resulting in constitutively active Bcr-abl fusion protein. | Turkish Journal of Biology Turk J Biol (2014) 38: 806-816 © TÜBİTAK doi:10.3906/biy-1405-21 http://journals.tubitak.gov.tr/biology/ Review Article Multidrug resistance in chronic myeloid leukemia 1 1 1 2 1, Miray ÜNLÜ , Yağmur KİRAZ , Fatma Necmiye KACI , Mehmet Ali ÖZCAN , Yusuf BARAN * Department of Molecular Biology and Genetics, Faculty of Science, İzmir Institute of Technology, İzmir, Turkey 2 Department of Hematology, Faculty of Medicine, Dokuz Eylül University, İzmir, Turkey 1 Received: 08.05.2014 Accepted: 01.09.2014 Published Online: 24.11.2014 Printed: 22.12.2014 Abstract: Chronic myeloid leukemia (CML) is characterized by the accumulation of Philadelphia chromosome-positive (Ph+) myeloid cells. Ph+ cells occur via a reciprocal translocation between the long arms of chromosomes 9 and 22 resulting in constitutively active Bcr-abl fusion protein. Tyrosine kinase inhibitors (TKIs) are used against the kinase activity of Bcr-abl fusion protein for the effective treatment of CML. However, the development of drug resistance, directed by different genetic mechanisms, is the major problem of clinical applications of TKIs. These mechanisms include mutations in the TKI binding site of Bcr-abl, overexpression of Bcr-abl, overexpression of ATP binding cassette transporters, aberrant ceramide metabolism, inhibition of apoptosis, and changes in expression levels of microRNAs. Recently, many studies have focused on understanding the molecular mechanisms of drug resistance in cancer while targeting therapies providing reversal of resistance. Cancer stem cells also have roles in tumor initiation, maintenance, progression, metastasis, and drug resistance. Uncovering the mechanisms of drug resistance can provide more efficient treatment of cancer since these findings may provide novel targets for a complete cure. In this review, we discuss recent findings on the mechanisms of multidrug resistance and its reversal in CML. Key words: Chronic myeloid leukemia, .