For COVID-19 vaccine updates, please review our information guide. For patient eligibility and scheduling availability, please visit VaccineTogetherNY.org.

A multifactorial role for P. falciparum malaria in endemic Burkitt's lymphoma pathogenesis.

TitleA multifactorial role for P. falciparum malaria in endemic Burkitt's lymphoma pathogenesis.
Publication TypeJournal Article
Year of Publication2014
AuthorsTorgbor C, Awuah P, Deitsch K, Kalantari P, Duca KA, Thorley-Lawson DA
JournalPLoS Pathog
Volume10
Issue5
Paginatione1004170
Date Published2014 May
ISSN1553-7374
KeywordsAnimals, Burkitt Lymphoma, Cell Line, Epstein-Barr Virus Infections, Herpesvirus 4, Human, Humans, Malaria, Falciparum, Plasmodium falciparum, Translocation, Genetic
Abstract

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.

DOI10.1371/journal.ppat.1004170
Alternate JournalPLoS Pathog.
PubMed ID24874410
PubMed Central IDPMC4038605
Grant ListR01 AI018757 / AI / NIAID NIH HHS / United States

Weill Cornell Medicine Microbiology and Immunology 1300 York Avenue, Box 62 New York, NY 10065 Phone: (212) 746-6505 Fax: (212) 746-8587