The Lmo2 Oncogene Initiates Leukemia in Mice by Inducing Thymocyte Self-Renewal

Abstract

It's All About Self-Renewal The Lmo2 oncogene was identified as a contributing factor in human T cell acute lymphoblastic leukemia (T-ALL) nearly two decades ago, but the gene rose to prominence in 2003 when its inadvertent activation by a retroviral vector was shown to cause leukemia in two patients in a gene therapy trial. The cellular mechanism by which the gene product of Lmo2 , a transcriptional regulator, induces T-ALL is poorly understood. Studying transgenic mice, McCormack et al. (p. 879 , published online 21 January) now show that Lmo2 confers self-renewal activity to committed T cells in the thymus without affecting their capacity for T cell differentiation. These self-renewing cells, which were detectable 8 months prior to the onset of overt leukemia in the mice, expressed genes in common with hematopoietic stem cells (HSCs), suggesting that Lmo2 might reactivate an HSC-specific transcriptional program.