Recurrent reciprocal RNA chimera involving YPEL5 and PPP1CB in chronic lymphocytic leukemia

Thirunavukkarasu Velusamy, Nallasivam Palanisamy, Shanker Kalyana-Sundaram, Anagh Anant Sahasrabuddhe, Christopher A. Maher, Daniel R. Robinson, David W. Bahler, Timothy T. Cornell, Thomas E. Wilson, Megan S. Lim, Arul M. Chinnaiyan, Kojo S.J. Elenitoba-Johnson

Research output: Contribution to journalArticle

27 Scopus citations

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.

Original languageEnglish
Pages (from-to)3035-3040
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number8
DOIs
StatePublished - Feb 19 2013

Keywords

  • B-lymphoid malignancy
  • Chimera splicing
  • Next-generation sequencing
  • Serine/threonine phosphatase PP1-beta catalytic subunit

Fingerprint Dive into the research topics of 'Recurrent reciprocal RNA chimera involving YPEL5 and PPP1CB in chronic lymphocytic leukemia'. Together they form a unique fingerprint.

  • Cite this

    Velusamy, T., Palanisamy, N., Kalyana-Sundaram, S., Sahasrabuddhe, A. A., Maher, C. A., Robinson, D. R., Bahler, D. W., Cornell, T. T., Wilson, T. E., Lim, M. S., Chinnaiyan, A. M., & Elenitoba-Johnson, K. S. J. (2013). Recurrent reciprocal RNA chimera involving YPEL5 and PPP1CB in chronic lymphocytic leukemia. Proceedings of the National Academy of Sciences of the United States of America, 110(8), 3035-3040. https://doi.org/10.1073/pnas.1214326110