| First Author | O'Neil J | Year | 2004 |
| Journal | Cancer Cell | Volume | 5 |
| Issue | 6 | Pages | 587-96 |
| PubMed ID | 15193261 | Mgi Jnum | J:91652 |
| Mgi Id | MGI:3047775 | Doi | 10.1016/j.ccr.2004.05.023 |
| Citation | O'Neil J, et al. (2004) TAL1/SCL induces leukemia by inhibiting the transcriptional activity of E47/HEB. Cancer Cell 5(6):587-96 |
| abstractText | 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. |
