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A key role for EZH2 and associated genes in mouse and human adult T-cell acute leukemia.

Simon C, Chagraoui J, Krosl J, Gendron P, Wilhelm B, Lemieux S, Boucher G, Chagnon P, Drouin S, Lambert R, Rondeau C, Bilodeau A, Lavallée S, Sauvageau M, Hébert J, Sauvageau G

The Leucegene Group, Institute for Research in Immunology and Cancer, University of Montreal, Montreal, Quebec H3T 1J4, Canada;

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.

Genes Dev. 2012;26(7):651-6.

Pubmed ID: 22431509

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