Advances in Brief scid Thymocytes with TCR Gene Rearrangements Are Targets for the Oncogenic Effect of SCL and LMO1 Transgenes

SCL and LMO1 were both discovered by virtue of their activation by chromosomal translocation in patients with T-cell acute lymphoblastic leukemia (T-ALL). Overexpression of SCL and LMO1 in the thymus of transgenic mice leads to T-ALL at a young age. scid (severe combined immunodeficient) mice are unable to efficiently recombine antigen receptor genes and consequently display a developmental block at the CD4CD8to CD4 CD8 transition. To test the hypothesis that this developmental block would protect SCL/LMO1 transgenic mice from developing T-ALL, we crossed the SCL and LMO1 transgenes onto a scid background. The age of onset for T-ALL in the SCL/LMO1/scid mice was significantly delayed (P < 0.001) compared with SCL/LMO1/wild-type mice. Intriguingly, all of the SCL/LMO1/scid malignancies displayed clonal, in-frame TCR gene rearrangements. Taken together, these findings suggest that the “leaky” scid thymocyte that undergoes a productive TCR gene rearrangement is susceptible to the oncogenic action of SCL and LMO1 and additionally suggests that TCR gene rearrangements may be required for the oncogenic action of SCL and LMO1.