GSBS Student Publications


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

UMMS Affiliation

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



Document Type


Medical Subject Headings

Animals; Antigens, CD4; Antigens, CD5; Apoptosis; Basic Helix-Loop-Helix Transcription Factors; Blotting, Northern; Blotting, Western; Chromatin; DNA-Binding Proteins; Flow Cytometry; Immunophenotyping; Intracellular Signaling Peptides and Proteins; Loss of Heterozygosity; Mice; Mice, Transgenic; Mutation; Oligonucleotide Array Sequence Analysis; Oncogene Proteins, Fusion; Precipitin Tests; Precursor Cell Lymphoblastic Leukemia-Lymphoma; TCF Transcription Factors; Thymus Gland; Time Factors; Transcription Factors; *Transcription, Genetic


Life Sciences | Medicine and Health Sciences


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.

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

DOI of Published Version


Related Resources

Link to article in PubMed

Journal Title

Cancer cell

PubMed ID