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

被引：218

作者：

Simon, Camille ^{[1
]}

Chagraoui, Jalila ^{[1
]}

Krosl, Jana ^{[1
]}

Gendron, Patrick ^{[1
]}

Wilhelm, Brian ^{[1
]}

Lemieux, Sebastien ^{[1
]}

Boucher, Genevieve ^{[1
]}

Chagnon, Pierre ^{[1
]}

Drouin, Simon ^{[1
]}

Lambert, Raphaelle ^{[1
]}

Rondeau, Claude ^{[2
]}

Bilodeau, Annie ^{[2
]}

Lavallee, Sylvie ^{[2
]}

Sauvageau, Martin ^{[1
]}

Hebert, Josee ^{[1
,2
,3
,4
]}

Sauvageau, Guy ^{[1
,2
,3
,4
]}

机构：

[1] Univ Montreal, Inst Res Immunol & Canc, Leucegene Grp, Montreal, PQ H3T 1J4, Canada

[2] Maisonneuve Rosemont Hosp, Leukemia Cell Bank Quebec, Montreal, PQ H1T 2M4, Canada

[3] Maisonneuve Rosemont Hosp, Div Hematol Oncol, Montreal, PQ H1T 2M4, Canada

[4] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada

来源：

GENES & DEVELOPMENT | 2012年 / 26卷 / 07期

关键词：

T-ALL; EZH2; PRC2; leukemia; JARID2; DNMT3A; REPRESSIVE COMPLEX 2; HEMATOPOIETIC STEM; SOMATIC MUTATIONS; POLYCOMB; PROTEINS; EED; INACTIVATION; PRC2;

D O I：

10.1101/gad.186411.111

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

In this study, we show the high frequency of spontaneous gamma delta 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.

引用

页码：651 / 656

页数：6

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