1. The Lmo2 oncogene initiates leukemia in mice by inducing thymocyte self-renewal
- Author
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McCormack, Matthew P., Young, Lauren F., Vasudevan, Sumitha, de Graaf, Carolyn A., Codrington, Rosalind, Rabbitts, Terence H., Jane, Stephen M., and Curtis, David J.
- Subjects
Thymoma -- Development and progression ,Cancer cells -- Properties ,Leukemia -- Development and progression ,Oncogenes -- Properties ,Science and technology - Abstract
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 ceil fate mapping to study mice in which the Lmo2 gene was constitutively expressed in the thymus. Lmo2 induced self-renewal of committed T ceiLs 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. 10.1126/science.1182378
- Published
- 2010
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