| First Author | Smith S | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 1 | Pages | e85883 |
| PubMed ID | 24465765 | Mgi Jnum | J:212335 |
| Mgi Id | MGI:5578674 | Doi | 10.1371/journal.pone.0085883 |
| Citation | Smith S, et al. (2014) LIM domain only-2 (LMO2) induces T-cell leukemia by two distinct pathways. PLoS One 9(1):e85883 |
| abstractText | The LMO2 oncogene is deregulated in the majority of human T-cell leukemia cases and in most gene therapy-induced T-cell leukemias. We made transgenic mice with enforced expression of Lmo2 in T-cells by the CD2 promoter/enhancer. These transgenic mice developed highly penetrant T-ALL by two distinct patterns of gene expression: one in which there was concordant activation of Lyl1, Hhex, and Mycn or alternatively, with Notch1 target gene activation. Most strikingly, this gene expression clustering was conserved in human Early T-cell Precursor ALL (ETP-ALL), where LMO2, HHEX, LYL1, and MYCN were most highly expressed. We discovered that HHEX is a direct transcriptional target of LMO2 consistent with its concordant gene expression. Furthermore, conditional inactivation of Hhex in CD2-Lmo2 transgenic mice markedly attenuated T-ALL development, demonstrating that Hhex is a crucial mediator of Lmo2's oncogenic function. The CD2-Lmo2 transgenic mice offer mechanistic insight into concordant oncogene expression and provide a model for the highly treatment-resistant ETP-ALL subtype. |
