The Journal of Experimental Medicine
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Published online 16 October 2000.
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© The Rockefeller University Press, 0022-1007/2000/10/1183/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 8, October 16, 2000 1183-1190

Brief Definitive Report

Burkitt Lymphoma in the Mouse

Alexander L. Kovalchuka, Chen-Feng Qib, Ted A. Torreyb, Lekidelu Taddesse-Heathb, Lionel Feigenbaumc, Sung Sup Parka, Armin Gerbitzd, Gustav Klobecke, Konstanze Hoertnageld, Axel Polackd, Georg W. Bornkammd, Siegfried Janza, and Herbert C. Morse, IIIb

a Laboratory of Genetics, National Cancer Institute,
b Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892
c Science Applications International Corporation (SAIC), Frederick Cancer Research Center, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702
d Institut für Klinische Molekularbiologie und Tumorgenetik, Munich 81377, Germany
e Institut für Physiologische Chemie der Ludwig-Maximilian Universität, Munich 80336, Germany
LIP, NIAID, 7 Center Dr., Rm. 7/304, MSC 0760, Bethesda, MD 20892-0760.301-402-0077301-496-6379

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.

Key Words: Burkitt lymphoma • locus control region • mouse lymphoma • MYC • translocation

© 2000 The Rockefeller University Press


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