H3K79 Methylation Profiles Define Murine and Human MLL-AF4 Leukemias

被引：425

作者：

Krivtsov, Andrei V. ^{[1
]}

Feng, Zhaohui ^{[1
]}

Lemieux, Madeleine E. ^{[2
]}

Faber, Joerg ^{[1
]}

Vempati, Sridhar ^{[1
,2
]}

Sinha, Amit U. ^{[1
,2
]}

Xia, Xiaobo ^{[2
]}

Jesneck, Jonathan ^{[2
]}

Bracken, Adrian P. ^{[4
]}

Silverman, Lewis B. ^{[1
,2
]}

Kutok, Jeffery L. ^{[3
]}

Kung, Andrew L. ^{[1
,2
]}

Armstrong, Scott A. ^{[1
,2
]}

机构：

[1] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA

[2] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[4] Univ Dublin Trinity Coll, Dept Genet, Smurfit Inst, Dublin 2, Ireland

来源：

CANCER CELL | 2008年 / 14卷 / 05期

关键词：

D O I：

10.1016/j.ccr.2008.10.001

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

We created a mouse model wherein conditional expression of an MII-AF4 fusion oncogene induces B precursor acute lymphoblastic (ALL) or acute myeloid leukemias (AML). Gene expression profile analysis of the ALL cells demonstrated significant overlap with human MLL-rearranged ALL. ChIP-chip analysis demonstrated histone H3 lysine 79 (H3K79) methylation profiles that correlated with MII-AF4-associated gene expression profiles in murine ALLs and in human MLL-rearranged leukemias. Human MLL-rearranged ALLs could be distinguished from other ALLs. by their H3K79 profiles, and suppression of the H3K79 methyltransferase DOT1L inhibited expression of critical MLL-AF4 target genes. We thus demonstrate that ectopic H3K79 methylation is a distinguishing feature of murine and human MLL-AF4 ALLs and is important for maintenance of MLL-AF4-driven gene expression.

引用

页码：355 / 368

页数：14

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