Selective leukemia cell death by activation of the double-stranded RNA-dependent protein kinase PKR
Deregulated activity of the BCR-ABL tyrosine kinase encoded by the Bcr-Abl oncogene represents an important therapeutic target for all the chronic myelogenous leukemia (CML) phases. In this study, we sought to identify targeted PKR activation by Bcr-Abl AS RNA, an anti-sense
RNA complementary to the unique mRNA fragments flanking the fusion point of Bcr-Abl, which can be used as an effective anti-leukemia strategy in K562 cells. Moreover, we observed expression of Bcr-Abl AS RNA in K562 cells which resulted in selective apoptosis induction through specific
activation of PKR, leading to phosphorylation of eIF2α, global inhibition of protein synthesis, caspase-8 activation and BAX up-regulation. The targeted PKR activation and induced apoptosis were reversed by the PKR inhibitor 2-aminopurine. Taken together, our results indicate that targeted
PKR activation led to selective apoptosis induction in K562 cells, which correlated with caspase-8 activity and enhanced expression of BAX.
Document Type: Research Article
Affiliations: 1: Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Chongqing 400016, P.R. China 2: Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China
Publication date: 01 January 2011
- The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases. - Editorial Board
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