Epidemiology: clues to the pathogenesis of Burkitt lymphoma
- 20 January 2012
- journal article
- review article
- Published by Wiley in British Journal of Haematology
- Vol. 156 (6), 744-756
- https://doi.org/10.1111/j.1365-2141.2011.09013.x
Abstract
The two major epidemiological clues to the pathogenesis of Burkitt lymphoma (BL) are the geographical association with malaria – BL incidence relates to the malaria transmission rate – and early infection by Epstein–Barr virus (EBV). Both agents cause B cell hyperplasia, which is almost certainly an essential component of lymphomagenesis in BL. The critical event in lymphomagenesis is the creation of a MYC translocation, bringing the MYC gene into juxtaposition with immunoglobulin genes and causing its ectopic expression, thereby driving the proliferation of BL cells. It is highly likely that such translocations are mediated by the activation‐induced cytidine deaminase (AID) gene, which is responsible for hypervariable region mutations as well as class switching. Stimulation of the Toll‐like receptor 9 by malaria‐associated agonists induces AID, providing a mechanism whereby malaria could directly influence BL pathogenesis. EBV‐containing cells must reach the memory cell compartment in order to survive throughout the life of the individual, which probably requires traversal of the germinal centre. Normally, cells that do not produce high affinity antibodies do not survive this passage, and are induced to undergo apoptosis. EBV, however, prevents this, and in doing so may also enhance the likelihood of survival of rare translocation‐containing cells.Keywords
This publication has 78 references indexed in Scilit:
- Epstein–Barr virus and its role in the pathogenesis of Burkitt's lymphoma: An unresolved issueSeminars in Cancer Biology, 2009
- Restricting activation-induced cytidine deaminase tumorigenic activity in B lymphocytesImmunology, 2009
- A Molecular Link between Malaria and Epstein–Barr Virus ReactivationPLoS Pathogens, 2007
- A longitudinal and prospective study of Epstein-Barr virus load in AIDS-related non-Hodgkin lymphomaJournal of Clinical Virology, 2006
- The great MYC escape in tumorigenesisCancer Cell, 2005
- Immunoglobulin gene analysis reveals 2 distinct cells of origin for EBV-positive and EBV-negative Burkitt lymphomasBlood, 2005
- Burkitt lymphoma in Papua, New Guinea.British Journal of Cancer, 1967
- An Epidemiologic Approach to the Lymphomas of African Children and Burkitt's Sarcoma of the JawsPerspectives in Biology and Medicine, 1964
- A Children's Cancer Dependent on Climatic FactorsNature, 1962
- A sarcoma involving the jaws in african childrenBritish Journal of Surgery, 1958