Selection Against PUMA Gene Expression in Myc-driven B-cell Lymphomagenesis

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2008 Jun 25

PMID 18573879

Citations 84

Authors

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

Affiliations

Soon will be listed here.

Abstract

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 Emu-Myc mouse model of Burkitt lymphoma accelerates lymphomagenesis and that approximately 75% of Emu-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.

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