The Role of miR-15a and miR-16-1 in the Pathogenesis of Chronic Lymphocytic Leukemia, and the Importance of microRNAs in Targeted Therapies.

Abstract

Objectives: Chronic lymphocytic leukemia (CLL) is the most common type of hematological cancer diagnosed in human adults; however, it has been linked with a series of chromosomal abnormalities, the most common being deletion of 13q14. This chromosomal alteration leads to the deletion of the miR-15/16 cluster, as well as downregulation of DLEU7. Deletion of miR-15a and miR-16-1 causes overexpression of BCL2, an apoptosis suppressing protein, while the deletion of DLEU7 activates the NF-kB pathway. Both lead to the development of a pro-proliferative phenotype, an inhibition of apoptosis and prolonged cell life. This is the basis of the pathogenesis of indolent CLL where these pathways present themselves as essential targets for pharmacological therapy. Since BCL2 is, arguably, the most important factor in the pathogenesis of CLL, BCL2 inhibitors are beginning to acquire more relevance regarding targeted therapies for patients with CLL. Here we review the role of miR-15a and miR-16-1 in the pathogenesis of chronic lymphocytic leukemia, and the importance of microRNAs in targeted therapies.