| First Author | McCormack MP | Year | 2010 |
| Journal | Science | Volume | 327 |
| Issue | 5967 | Pages | 879-83 |
| PubMed ID | 20093438 | Mgi Jnum | J:156935 |
| Mgi Id | MGI:4422114 | Doi | 10.1126/science.1182378 |
| Citation | McCormack MP, et al. (2010) The lmo2 oncogene initiates leukemia in mice by inducing thymocyte self-renewal. Science 327(5967):879-83 |
| abstractText | The LMO2 oncogene causes a subset of human T cell acute lymphoblastic leukemias (T-ALL), including four cases that arose as adverse events in gene therapy trials. To investigate the cellular origin of LMO2-induced leukemia, we used cell fate mapping to study mice in which the Lmo2 gene was constitutively expressed in the thymus. Lmo2 induced self-renewal of committed T cells in the mice more than 8 months before the development of overt T-ALL. These self-renewing cells retained the capacity for T cell differentiation but expressed several genes typical of hematopoietic stem cells (HSCs), suggesting that Lmo2 might reactivate an HSC-specific transcriptional program. Forced expression of one such gene, Hhex, was sufficient to initiate self-renewal of thymocytes in vivo. Thus, Lmo2 promotes the self-renewal of preleukemic thymocytes, providing a mechanism by which committed T cells can then accumulate additional genetic mutations required for leukemic transformation. |
