Burkitt lymphoma in the mouse

Chromosomal translocations juxtaposing the MYC protooncogene with regulator y sequences of immunoglobulin (Ig) H chain or kappa (Ig kappa) or lambda (I g lambda) L chain genes and effecting deregulated expression of MYC are the hallmarks of human Burkitt lymphoma (BL). Here we report that lymphomas wi th striking similarities to BL develop in mice bearing a mutated human MYC gene controlled by a reconstructed Ig lambda locus encompassing all the ele ments required for establishment of locus control in vitro. Diffusely infil trating lymphomas with a typical starry sky appearance occurred in multiple founders and an established line, indicating independence from positional effects. Monoclonal IgM(+)CD5(-)CD23(-) tumors developed from an initially polyclonal population of B cells. These results demonstrate chat the phenot ype of B lineage lymphomas induced by MYC dysregulation is highly dependent on cooperativity among the regulatory elements that govern expression of t he protooncogene and provide a new system for studying the pathogenesis of BL.