Multidrug resistance in chronic myeloid leukemia

Authors : Miray ÜNLÜ, Yağmur KİRAZ, Fatma Necmiye KACI, Mehmet Ali ÖZCAN, Yusuf BARAN

Pages : 806-816

Doi:10.3906/biy-1405-21

View : 22 | Download : 11

Publication Date : 2014-12-01

Article Type : Research Paper

Abstract :Chronic myeloid leukemia insert ignore into journalissuearticles values(CML); is characterized by the accumulation of Philadelphia chromosome-positive insert ignore into journalissuearticles values(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 insert ignore into journalissuearticles values(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.
Keywords : Chronic myeloid leukemia, drug resistance, tyrosine kinase inhibitor, Bcr abl