Crosstalk between BCR/ABL and RNAi

Abstract

Chronic myeloid leukemia (CML) is a malignant disease of progenitor myeloid cells caused by chromosomal translocation that results in the forming of diminutive Philadephia chromosome that harbors BCR/ABL fusion oncogene. The product of this oncogene, a tyrosine kinase, alters several important regulatory pathways related to cell growth and differentiation thus leading to cancer transformation. Major form of CML therapy is based on tyrosine kinase inhibitors, first of all imatinib (IM). Some patients develop resistance to IM in the course of treatment. In the process of leukemogenesis the activity of miRNAs – one of groups of RNAs involved in RNA interference (RNAi) – is altered. Signatures of altered miRNAs activity may serve as a prognostic factor in the development and therapy of several diseases. Moreover, other group of RNAs involved in RNAi – siRNA – might be valuable addition to array of specific therapeutics targeted the BCR/ABL kinase.