A multifactorial role for P. falciparum malaria in endemic Burkitt's lymphoma pathogenesis. Academic Article uri icon

Overview

MeSH

  • Animals
  • Cell Line
  • Humans
  • Translocation, Genetic

MeSH Major

  • Burkitt Lymphoma
  • Epstein-Barr Virus Infections
  • Herpesvirus 4, Human
  • Malaria, Falciparum
  • Plasmodium falciparum

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.

publication date

  • May 2014

has subject area

  • Animals
  • Burkitt Lymphoma
  • Cell Line
  • Epstein-Barr Virus Infections
  • Herpesvirus 4, Human
  • Humans
  • Malaria, Falciparum
  • Plasmodium falciparum
  • Translocation, Genetic

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4038605

Digital Object Identifier (DOI)

  • 10.1371/journal.ppat.1004170

PubMed ID

  • 24874410

Additional Document Info

start page

  • e1004170

volume

  • 10

number

  • 5