A key role for EZH2 and associated genes in mouse and human adult T-cell acute leukemia
- Camille Simon1,
- Jalila Chagraoui1,
- Jana Krosl1,
- Patrick Gendron1,
- Brian Wilhelm1,
- Sébastien Lemieux1,
- Geneviève Boucher1,
- Pierre Chagnon1,
- Simon Drouin1,
- Raphaëlle Lambert1,
- Claude Rondeau2,
- Annie Bilodeau2,
- Sylvie Lavallée2,
- Martin Sauvageau1,
- Josée Hébert1,2,3,4,5 and
- Guy Sauvageau1,2,3,4,5
- 1The Leucegene Group, Institute for Research in Immunology and Cancer, University of Montreal, Montreal, Quebec H3T 1J4, Canada;
- 2Leukemia Cell Bank of Quebec, Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada;
- 3Division of Hematology-Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada;
- 4Department of Medicine, University of Montreal, Montreal, Quebec H3C 3J7, Canada
Abstract
In this study, we show the high frequency of spontaneous γδ T-cell leukemia (T-ALL) occurrence in mice with biallelic deletion of enhancer of zeste homolog 2 (Ezh2). Tumor cells show little residual H3K27 trimethylation marks compared with controls. EZH2 is a component of the PRC2 Polycomb group protein complex, which is associated with DNA methyltransferases. Using next-generation sequencing, we identify alteration in gene expression levels of EZH2 and acquired mutations in PRC2-associated genes (DNMT3A and JARID2) in human adult T-ALL. Together, these studies document that deregulation of EZH2 and associated genes leads to the development of mouse, and likely human, T-ALL.
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Footnotes
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↵5 Corresponding authors.
E-mail guy.sauvageau{at}umontreal.ca.
E-mail josee.hebert{at}umontreal.ca.
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.186411.111.
- Received December 27, 2011.
- Accepted February 22, 2012.
- Copyright © 2012 by Cold Spring Harbor Laboratory Press
