Deregulated expression of the Myc cellular oncogene drives development of mouse "Burkitt-like" lymphomas from naive B cells. Blood 2005 Mar 01;105(5):2135-7
Date
11/04/2004Pubmed ID
15522957DOI
10.1182/blood-2004-07-2573Scopus ID
2-s2.0-14944339170 (requires institutional sign-in at Scopus site) 34 CitationsAbstract
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.
Author List
Zhu D, Qi CF, Morse HC 3rd, Janz S, Stevenson FKAuthor
Siegfried Janz MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsB-Lymphocytes
Burkitt Lymphoma
Chromosomes, Mammalian
Gene Expression Regulation, Neoplastic
Genes, myc
Genetic Engineering
Germinal Center
Immunoglobulin Heavy Chains
Mice
Mice, Mutant Strains
Molecular Mimicry
Translocation, Genetic
