TAL1/SCL induces leukemia by inhibiting the transcriptional activity of E47/HEB

被引：155

作者：

O'Neil, J

Shank, J

Cusson, N

Murre, C

Kelliher, M ^{[1
]}

机构：

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

[2] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA

来源：

CANCER CELL | 2004年 / 5卷 / 06期

关键词：

D O I：

10.1016/j.ccr.2004.05.023

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Activation of the basic-helix-loop-helix (bHLH) gene TAL1 (or SCL) is a frequent gain-of-function mutation in T cell acute lymphoblastic leukemia (T-ALL). To provide genetic evidence that tal1/scl induces leukemia by interfering with E47 and HEB, we expressed tal1/scl in an E2A or HEB heterozygous background. These mice exhibit disease acceleration and perturbed thymocyte development due to repression of E47/HEB target genes. In tal1/scl thymocytes, we find the corepressor mSin3A bound to the CD4 enhancer, whereas an E47/HEB/p300 complex is detected in wild-type thymocytes. Furthermore, tal1/scl tumors are sensitive to pharmacologic inhibition of HDAC and undergo apoptosis. These data demonstrate that tall/scl induces leukemia by repressing E47/HEB and suggest that HDAC inhibitors may prove efficacious in T-ALL patients who express TAL1/SCL.

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页码：587 / 596

页数：10

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