The Lmo2 oncogene initiates leukemia in mice by inducing thymocyte self-renewal
- PMID: 20093438
- DOI: 10.1126/science.1182378
The Lmo2 oncogene initiates leukemia in mice by inducing thymocyte self-renewal
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 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.
Comment in
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The thymus under siege: Lmo2 induces precancerous stem cells in a mouse model of T-ALL.Cell Cycle. 2010 Jun 15;9(12):2267-8. doi: 10.4161/cc.9.12.12074. Epub 2010 Jun 15. Cell Cycle. 2010. PMID: 20519951 No abstract available.
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