Author/Authors :
Sander، نويسنده , , Sandrine and Calado، نويسنده , , Dinis P. and Srinivasan، نويسنده , , Lakshmi and Kِchert، نويسنده , , Karl and Zhang، نويسنده , , Baochun and Rosolowski، نويسنده , , Maciej and Rodig، نويسنده , , Scott J. and Holzmann، نويسنده , , Karlheinz and Stilgenbauer، نويسنده , , Stephan and Siebert، نويسنده , , Reiner and Bullinger، نويسنده , , Lars and Rajewsky، نويسنده , , Klaus، نويسنده ,
Abstract :
Summary
kitt lymphoma (BL), a germinal center B-cell-derived tumor, the pro-apoptotic properties of c-MYC must be counterbalanced. Predicting that survival signals would be delivered by phosphoinositide-3-kinase (PI3K), a major survival determinant in mature B cells, we indeed found that combining constitutive c-MYC expression and PI3K activity in germinal center B cells of the mouse led to BL-like tumors, which fully phenocopy human BL with regard to histology, surface and other markers, and gene expression profile. The tumors also accumulate tertiary mutational events, some of which are recurrent in the human disease. These results and our finding of recurrent PI3K pathway activation in human BL indicate that deregulated c-MYC and PI3K activity cooperate in BL pathogenesis.
