title: A multifactorial role for P. falciparum malaria in endemic Burkitt's lymphoma pathogenesis.
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.
authors.affiliation: Tufts University School of Medicine, Boston, Massachusetts, United States of America; Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology (KNUST) and Kumasi Centre for Collaborative Research, Kumasi, Ghana.
authors.forename: Charles
authors.initials: C
authors.lastname: Torgbor
authors.affiliation: EENT Clinic, Komfo Anokye Teaching Hospital (KATH) and PAKS Hospital, Kumasi, Ghana.
authors.forename: Peter
authors.initials: P
authors.lastname: Awuah
authors.affiliation: Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Kirk
authors.initials: K
authors.lastname: Deitsch
authors.affiliation: University of Massachusetts Medical School, Department of Medicine, Division of Immunology and Infectious Diseases, Worcester, Massachusetts, United States of America.
authors.forename: Parisa
authors.initials: P
authors.lastname: Kalantari
authors.affiliation: Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology (KNUST) and Kumasi Centre for Collaborative Research, Kumasi, Ghana.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Duca
authors.affiliation: Tufts University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: David A
authors.initials: DA
authors.lastname: Thorley-Lawson
mesh_terms: D000818:Animals; D002051:Burkitt Lymphoma / Q000276:immunology* / Q000469:parasitology / Q000821:virology; D002460:Cell Line; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000276:immunology*; D004854:Herpesvirus 4, Human; D006801:Humans; D016778:Malaria, Falciparum / Q000235:genetics / Q000276:immunology*; D010963:Plasmodium falciparum; D014178:Translocation, Genetic / Q000235:genetics / Q000502:physiology