TAL1/SCL induces leukemia by inhibiting the transcriptional activity of E47/HEB
Graduate School of Biomedical Sciences; Department of Cancer Biology; Department of Molecular Genetics and Microbiology
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.
DOI of Published Version
Cancer Cell. 2004 Jun;5(6):587-96. Link to article on publisher's site
O'Neil, Jennifer Elinor; Shank, Jennifer; Cusson, Nicole; Murre, Cornelis; and Kelliher, Michelle, "TAL1/SCL induces leukemia by inhibiting the transcriptional activity of E47/HEB" (2004). GSBS Student Publications. 914.