Department of Medicine, Division of Immunology and Infectious Diseases
Immunology of Infectious Disease | Immunopathology | Neoplasms | Parasitic Diseases | Pediatrics
Endemic Burkitt's lymphoma (eBL) arises from the germinal center (GC). It is a common tumor of young children in tropical Africa and its occurrence is closely linked geographically with the incidence of P. falciparum malaria. This association was noted more than 50 years ago. Since then we have learned that eBL contains the oncogenic herpes virus Epstein-Barr virus (EBV) and a defining translocation that activates the c-myc oncogene. However the link to malaria has never been explained. Here we provide evidence for a mechanism arising in the GC to explain this association. Accumulated evidence suggests that eBL arises in the GC when deregulated expression of AID (Activation-induced cytidine deaminase) causes a c-myc translocation in a cell latently infected with Epstein-Barr virus (EBV). Here we show that P. falciparum targets GC B cells via multiple pathways to increase the risk of eBL. 1. It causes deregulated expression of AID, thereby increasing the risk of a c-myc translocation. 2. It increases the number of B cells transiting the GC. 3. It dramatically increases the frequency of these cells that are infected with EBV and therefore protected from c-myc induced apoptosis. We propose that these activities combine synergistically to dramatically increase the incidence of eBL in individuals infected with malaria.
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© 2014 Torgbor et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
PLoS Pathog. 2014 May 29;10(5):e1004170. doi: 10.1371/journal.ppat.1004170. eCollection 2014. Link to article on publisher's site
Torgbor, Charles; Awuah, Peter; Deitsch, Kirk; Kalantari, Parisa; Duca, Karen A.; and Thorley-Lawson, David A, "A multifactorial role for P. falciparum malaria in endemic Burkitt's lymphoma pathogenesis" (2014). University of Massachusetts Medical School Faculty Publications. 415.
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