Core Transcriptional Regulatory Circuit Controlled by the TAL1 Complex in Human T Cell Acute Lymphoblastic Leukemia

被引：254

作者：

Sanda, Takaomi ^{[1
]}

Lawton, Lee N. ^{[2
]}

Barrasa, M. Inmaculada ^{[2
]}

Fan, Zi Peng ^{[2
,3
]}

Kohlhammer, Holger ^{[5
]}

Gutierrez, Alejandro ^{[1
,6
]}

Ma, Wenxue ^{[7
,8
]}

Tatarek, Jessica ^{[9
]}

Ahn, Yebin ^{[1
]}

Kelliher, Michelle A. ^{[7
,8
]}

Jamieson, Catriona H. M. ^{[7
,8
]}

Staudt, Louis M. ^{[5
]}

Young, Richard A. ^{[2
,4
]}

Look, A. Thomas ^{[1
,6
]}

机构：

[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA

[2] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[3] MIT, Computat & Syst Biol Program, Cambridge, MA 02142 USA

[4] MIT, Dept Biol, Cambridge, MA 02142 USA

[5] NCI, Metab Branch, Bethesda, MD 20892 USA

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

[7] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA

[8] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA

[9] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA

来源：

CANCER CELL | 2012年 / 22卷 / 02期

基金：

美国国家卫生研究院; 日本学术振兴会;

关键词：

GENOME-WIDE ANALYSIS; GENE-EXPRESSION; TARGET GENE; BINDING; ALPHA; E2A; SCL; PROTEINS; ONCOGENE; NETWORKS;

D O I：

10.1016/j.ccr.2012.06.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The oncogenic transcription factor TAL1/SCL is aberrantly expressed in over 40% of cases of human T cell acute lymphoblastic leukemia (T-ALL), emphasizing its importance in the molecular pathogenesis of T-ALL. Here we identify the core transcriptional regulatory circuit controlled by TAL1 and its regulatory partners HEB, E2A, LMO1/2, GATA3, and RUNX1. We show that TAL1 forms a positive interconnected autoregulatory loop with GATA3 and RUNX1 and that the TAL1 complex directly activates the MYB oncogene, forming a positive feed-forward regulatory loop that reinforces and stabilizes the TAL1-regulated oncogenic program. One of the critical downstream targets in this circuitry is the TRIB2 gene, which is oppositely regulated by TAL1 and E2A/HEB and is essential for the survival of T-ALL cells.

引用

页码：209 / 221

页数：13

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