Of mice and men: how an oncogene transgresses the limits and predisposes to T cell acute lymphoblastic leukemia.

The gene encoding LIM-only 2 (LMO2), an oncogenic transcription factor, is frequently activated in T cell acute lymphoblastic leukemia (T-ALL), but how LMO2 transforms primary hematopoietic cells to induce T-ALL remains an open question. McCormack et al. now show that, in mice, Lmo2 confers self-renewal potential on normally nonrenewing thymocyte progenitor cells, and this property is maintained over four serial transplantations when the cells are transplanted into irradiated mice that lack thymocytes. These leukemia-initiating cells are resistant to irradiation, indicating the need to develop new therapeutic drugs that specifically target the oncogene itself.