GSBS Student Publications

Title

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

Publication Date

2004-06-15

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Cancer Biology; Department of Molecular Genetics and Microbiology

Document Type

Article

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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 tal1/scl induces leukemia by repressing E47/HEB and suggest that HDAC inhibitors may prove efficacious in T-ALL patients who express TAL1/SCL.

DOI of Published Version

10.1016/j.ccr.2004.05.023

Source

Cancer Cell. 2004 Jun;5(6):587-96. Link to article on publisher's site

Journal/Book/Conference Title

Cancer cell

Related Resources

Link to article in PubMed

PubMed ID

15193261

Share

COinS