Alternative Splicing in Chronic Myeloid Leukemia (CML): A Novel Therapeutic Target?

Alternative Splicing in Chronic Myeloid Leukemia (CML): A Novel Therapeutic Target?
Curr Cancer Drug Targets. 2013 Jul 30;
Authors: Adamia S, Pilarski PM, Natan MB, Stone RM, Griffin JD
Abstract
Although the imatinib based therapy of chronic myeloid leukemia (CML) represents a triumph of medicine, not all patients with CML benefit from this drug due to the development of resistance and intolerance. The interruption of imatinib treatment is often followed by clinical relapse, suggesting a failure in the killing of residual leukaemic stem cells. There is need to identify alternative selective molecular targets for this disease and develop more effective therapeutic approaches. Alternative pre-mRNA splicing (AS) is an epigenetic process that greatly diversifies the repertoire of the transcriptome. AS orchestrates interactions between various types of proteins and between proteins and nucleic acids. Changes caused by individual splicing events in the cells are small, however, "splicing programs" typically react to these individual changes with considerable effects in cell proliferation, cell survival, and apoptosis. Current evidence suggests a pivotal role of AS in leukemias, particularly in myelodisplastic syndrome (MDS) and chronic lymphocyte leukemia (CLL). From these studies and studies in other malignances, it is clear that splicing abnormalities play a significant role in malignant transformation. Evaluation of AS events in CML can be used t...

Source: Current Cancer Drug Targets - July 30, 2013 Category: Cancer & Oncology Authors: Adamia S, Pilarski PM, Natan MB, Stone RM, Griffin JD Tags: Curr Cancer Drug Targets Source Type: research