| First Author | Chervinsky DS | Year | 1999 |
| Journal | Mol Cell Biol | Volume | 19 |
| Issue | 7 | Pages | 5025-35 |
| PubMed ID | 10373552 | Mgi Jnum | J:55891 |
| Mgi Id | MGI:1339525 | Doi | 10.1128/mcb.19.7.5025 |
| Citation | Chervinsky DS, et al. (1999) Disordered T-cell development and T-cell malignancies in SCL LMO1 double-transgenic mice: parallels with E2A-deficient mice. Mol Cell Biol 19(7):5025-35 |
| abstractText | The gene most commonly activated by chromosomal rearrangements in patients with T-cell acute lymphoblastic leukemia (T-ALL) is SCL/tal. In collaboration with LMO1 or LMO2, the thymic expression of SCL/tal leads to T-ALL at a young age with a high degree of penetrance in transgenic mice. We now show that SCL LMO1 double-transgenic mice display thymocyte developmental abnormalities in terms of proliferation, apoptosis, clonality, and immunophenotype prior to the onset of a frank malignancy. At 4 weeks of age, thymocytes from SCL LMO1 mice show 70% fewer total thymocytes, with increased rates of both proliferation and apoptosis, than control thymocytes. At this age, a clonal population of thymocytes begins to populate the thymus, as evidenced by oligoclonal T-cell-receptor gene rearrangements. Also, there is a dramatic increase in immature CD44(+) CD25(-) cells, a decrease in the more mature CD4(+) CD8(+) cells, and development of an abnormal CD44(+) CD8(+) population. An identical pattern of premalignant changes is seen with either a full-length SCL protein or an amino-terminal truncated protein which lacks the SCL transactivation domain, demonstrating that the amino-terminal portion of SCL is not important for leukemogenesis. Lastly, we show that the T-ALL which develop in the SCL LMO1 mice are strikingly similar to those which develop in E2A null mice, supporting the hypothesis that SCL exerts its oncogenic action through a functional inactivation of E proteins. |
