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.