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

• Published in: Blood 2005-03, Vol.105 (5), p.2135-2137
• Main Authors: Zhu, Delin, Qi, Chen Feng, Morse, Herbert C., Janz, Siegfried, Stevenson, Freda K.
• Format: Article
• Language: English
• Subjects: Animals; B-Lymphocytes - pathology; Biological and medical sciences; Burkitt Lymphoma - etiology; Burkitt Lymphoma - genetics; Chromosomes, Mammalian; Gene Expression Regulation, Neoplastic; Genes, myc; Genetic Engineering; Germinal Center; Hematologic and hematopoietic diseases; Immunoglobulin Heavy Chains - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Mice; Mice, Mutant Strains; Molecular Mimicry; Translocation, Genetic
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2004-07-2573

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 Eμ, 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 VH 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.