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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Chinnaiyan, Arul M. Kalyana-sundaram, Shanker Robinson, Daniel R. Velusamy, Thirunavukkarasu Wilson, Thomas E. Elenitoba-johnson, Kojo S. J. Sahasrabuddhe, Anagh Anant Palanisamy, Nallasivam Maher, Christopher A. Cornell, Timothy T. Bahler, David W. Lim, Megan S. |
| Description | Author Affiliation: Velusamy T ( Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.); |
| Abstract | Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults in the Western hemisphere. Tumor-specific chromosomal translocations, characteristic findings in several human malignancies that directly lead to malignant transformation, have not been identified in CLL. Using paired-end transcriptome sequencing, we identified recurrent and reciprocal RNA chimeras involving yippee like 5 (YPEL5) and serine/threonine-protein phosphatase PP1-beta-catalytic subunit (PPP1CB) in CLL. Two of seven index cases (28%) harbored the reciprocal RNA chimeras in our initial screening. Using quantitative real-time PCR (q real-time PCR), YPEL5/PPP1CB and PPP1CB/YPEL5 fusion transcripts were detected in 97 of 103 CLL samples (95%) but not in paired normal samples, benign lymphocytes, or various unrelated cancers. Whole-genome sequencing and Southern blotting demonstrated no evidence for a genomic fusion between YPEL5 and PPP1CB. YPEL5/PPP1CB chimera, when introduced into mammalian cells, expressed a truncated PPP1CB protein that demonstrated diminished phosphatase activity. PPP1CB silencing resulted in enhanced proliferation and colony formation of MEC1 and JVM3 cells, implying a role in the pathogenesis of mature B-cell leukemia. These studies uncover a potential role for recurrent RNA chimeras involving phosphatases in the pathogenesis of a common form of leukemia. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 8 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cell Cycle Proteins Genetics Leukemia, Lymphocytic, Chronic, B-Cell Protein Phosphatase 1 RNA, Neoplasm Blotting, Southern Catalytic Domain Gene Fusion Real-Time Polymerase Chain Reaction Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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