Deregulated expression of the Myc cellular oncogene drives development of mouse "Burkitt-like" lymphomas from naive B cells

Zhu, Delin, Qi, Chen Feng, Morse, Herbert C., Janz, Siegfried and Stevenson, Freda K. (2005) Deregulated expression of the Myc cellular oncogene drives development of mouse "Burkitt-like" lymphomas from naive B cells. Blood, 105 (5), 2135-2137. (doi:10.1182/blood-2004-07-2573).

Abstract

Chromosomal translocations juxtaposing immunoglobulin (Ig) and MYC genes are the hallmarks of human Burkitt lymphoma (BL), with deregulated MYC expression being a critical factor in pathogenesis. By inserting an intact mouse Myc gene into the mouse genome, proximal to the Ig enhancer Emu, the effect of a precise mimic of the major t(8;14) translocation of human endemic BL (eBL) could be investigated. Knock-in mice developed IgM-positive B-cell tumors, with most being typical of eBL by histology and immunophenotype, including expression of the germinal center (GC)-associated protein, BCL6. Unlike eBL, however, analysis of Ig V(H) sequences revealed no significant level of somatic mutation. Thus, constitutive expression of Myc in the knock-in mice is apparently able to induce "Burkitt-like" lymphomas before antigen stimulation and formation of a GC. In contrast, human eBL development occurs in a GC or post-GC site with a likely contribution to pathogenesis from Epstein-Barr virus (EBV) and other epigenetic factors.

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Contributors

Author: Freda K. Stevenson

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