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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute Disease
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Animals
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Enhancer of Zeste Homolog 2 Protein
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Histone-Lysine N-Methyltransferase / genetics
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Histone-Lysine N-Methyltransferase / metabolism*
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Humans
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Leukemia-Lymphoma, Adult T-Cell / genetics
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Leukemia-Lymphoma, Adult T-Cell / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Polycomb Repressive Complex 2
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Polycomb-Group Proteins
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Protein Binding
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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DNA-Binding Proteins
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Polycomb-Group Proteins
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Repressor Proteins
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Transcription Factors
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EZH2 protein, human
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Enhancer of Zeste Homolog 2 Protein
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Ezh2 protein, mouse
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Histone-Lysine N-Methyltransferase
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Polycomb Repressive Complex 2