Overexpression of LMO2 causes aberrant human T-cell development in vivo by three potentially distinct cellular mechanisms

LMO2 overexpressing transgenic mouse models suggest an accumulation of immature T-cell progenitors in the thymus as main pre-leukemic event. The effects of LMO2 overexpression on human T-cell development in vivo, however, are unknown. Here we report studies of a humanized mouse model transplanted with LMO2 transduced human hematopoietic stem and progenitor cells. The effects of LMO2 overexpression were confined to the T-cell lineage although initially multipotent cells were transduced. Three effects of LMO2 on human T-cell development were observed: 1) a block at the DN/ISP stage, 2) an accumulation of CD4+CD8+ double positive CD3- cells and 3) an altered CD8/CD4 ratio with enhanced peripheral T lymphocytes

4

Wiekmeijer AS, Pike-Overzet K, Brugman MH, van Eggermond MC, Cordes M, de Haas EF, Li Y, Oole E, van IJcken WF, Egeler RM, Meijerink JP, Staal FJ