Downregulation of Bcr-Abl oncogene in Chronic Myeloid Leukemia (CML) by microRNAs in case of Imatinib resistance

Abstract

The well-known myeloproliferative malignancy, chronic myeloid leukemia (CML), causes due to the formation of short and modified Philadelphia chromosome having the Bcr-Abl oncogene. Many therapeutic approaches have been made for the treatment of CML, the best one was the development of Tyrosine Kinase Inhibitors (TKIs), mainly Imatinib. But after the development of mutation against Imatinib, researchers moved towards RNA interference (RNAi) of BCR-ABL mRNA via microRNAs. In this review, we identified 105 miRNAs by Target Scan, miRbase and miRNAMap, which target the proteins of CML signaling pathway. These are selected on the basis of their constitutive activation in the Bcr-Abl positive cell lines. Targeting these proteins by miRNAs might effectively enhance chemotherapy-induced cytotoxicity in CML cells. Out of these 105 miRNAs, 21 were found to commonly effective against those proteins. These 21 microRNAs may or may not have been studied in CML cases, but have been studied in other solid or myeloid tumors. This review might be helpful in extending the studies regarding regulation of CML signaling proteins by miRNAs.