Document Detail


Deregulated expression of the Myc cellular oncogene drives development of mouse "Burkitt-like" lymphomas from naive B cells.
MedLine Citation:
PMID:  15522957     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Delin Zhu; Chen Feng Qi; Herbert C Morse; Siegfried Janz; Freda K Stevenson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-11-02
Journal Detail:
Title:  Blood     Volume:  105     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-02-17     Completed Date:  2005-03-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2135-7     Citation Subset:  AIM; IM    
Affiliation:
Molecular Immunology Group, Tenovus Laboratory, Southampton University Hospitals Trust, Southampton SO16 6YD, United Kingdom. d.zhu@soton.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Animals
B-Lymphocytes / pathology*
Burkitt Lymphoma / etiology*,  genetics
Chromosomes, Mammalian
Gene Expression Regulation, Neoplastic*
Genes, myc*
Genetic Engineering
Germinal Center
Immunoglobulin Heavy Chains / genetics
Mice
Mice, Mutant Strains
Molecular Mimicry
Translocation, Genetic
Chemical
Reg. No./Substance:
0/Immunoglobulin Heavy Chains

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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