Deregulated expression of the Myc cellular oncogene drives development of mouse "Burkitt-like" lymphomas from naive B cells.
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.
Zhu
Delin
D
Molecular Immunology Group, Tenovus Laboratory, Southampton University Hospitals Trust, Southampton SO16 6YD, United Kingdom. d.zhu@soton.ac.uk
Qi
Chen Feng
CF
Morse
Herbert C
HC
Janz
Siegfried
S
Stevenson
Freda K
FK
D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology*; D002051:Burkitt Lymphoma / Q000209:etiology* / Q000235:genetics; D033481:Chromosomes, Mammalian; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D005818:Genetic Engineering; D018858:Germinal Center; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D018716:Molecular Mimicry; D014178:Translocation, Genetic
D007143:Immunoglobulin Heavy Chains