Selection against PUMA gene expression in Myc-driven B-cell lymphomagenesis

Sean P. Garrison, John R. Jeffers, Chunying Yang, Jonas A. Nilsson, Mark A. Hall, Jerold E. Rehg, Wen Yue, Jian Yu, Lin Zhang, Mihaela Onciu, Jeffery T. Sample, John L. Cleveland, Gerard P. Zambetti

Research output: Contribution to journalArticlepeer-review

120 Scopus citations


The p53 tumor suppressor pathway limits oncogenesis by inducing cell cycle arrest or apoptosis. A key p53 target gene is PUMA, which encodes a BH3-only proapoptotic protein. Here we demonstrate that Puma deletion in the Eμ-Myc mouse model of Burkitt lymphoma accelerates lymphomagenesis and that ∼75% of Eμ-Myc lymphomas naturally select against Puma protein expression. Furthermore, approximately 40% of primary human Burkitt lymphomas fail to express detectable levels of PUMA and in some tumors this is associated with DNA methylation. Burkitt lymphoma cell lines phenocopy the primary tumors with respect to DNA methylation and diminished PUMA expression, which can be reactivated following inhibition of DNA methyltransferases. These findings establish that PUMA is silenced in human malignancies, and they suggest PUMA as a target for the development of novel chemotherapeutics.

Original languageEnglish (US)
Pages (from-to)5391-5402
Number of pages12
JournalMolecular and cellular biology
Issue number17
StatePublished - Sep 2008

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology


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