Burkitt lymphoma in the mouse

• Published in: The Journal of experimental medicine Vol. 192; no. 8; pp. 1183 - 1190
• Main Authors: Kovalchuk, A L, Qi, C F, Torrey, T A, Taddesse-Heath, L, Feigenbaum, L, Park, S S, Gerbitz, A, Klobeck, G, Hoertnagel, K, Polack, A, Bornkamm, G W, Janz, S, Morse, 3rd, H C
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 16-10-2000
• Subjects: Animals; Brief Definitive Report; Burkitt Lymphoma - genetics; Burkitt Lymphoma - immunology; Burkitt Lymphoma - pathology; CD23 antigen; CD5 antigen; Disease Models, Animal; Exons; Genes, myc; Humans; Mice; Mice, Inbred C57BL; Mice, Transgenic; Proto-Oncogene Proteins c-myc - analysis; Proto-Oncogene Proteins c-myc - genetics; Spleen - immunology; Spleen - pathology
• ISSN: 0022-1007; 1540-9538; 1892-1007
• DOI: 10.1084/jem.192.8.1183

Chromosomal translocations juxtaposing the MYC protooncogene with regulatory sequences of immunoglobulin (Ig) H chain or kappa (Ig kappa) or lambda (Ig lambda) L chain genes and effecting deregulated expression of MYC are the hallmarks of human Burkitt lymphoma (BL). Here we report that lymphomas with striking similarities to BL develop in mice bearing a mutated human MYC gene controlled by a reconstructed Ig lambda locus encompassing all the elements required for establishment of locus control in vitro. Diffusely infiltrating 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 that the phenotype of B lineage lymphomas induced by MYC dysregulation is highly dependent on cooperativity among the regulatory elements that govern expression of the protooncogene and provide a new system for studying the pathogenesis of BL.