Epstein‐Barr virus and the pathogenesis of Burkitt's lymphoma: More questions than answers

Abstract

Burkitt's lymphoma (BL) was first described as a clinical entity in children in Central Africa by Denis Burkitt in 1958. The particular epidemiological features of this tumor initiated the search for a virus as the causative agent and led to the discovery of EpsteinBarr virus (EBV) by Epstein and coworkers in 1964. It became apparent in the seventies and eighties that the tumor is not restricted to Central Africa, but occurs with lesser incidence all over the world (sporadic BL) and is also particularly frequent in HIV infected individuals, and that not all BL cases are associated with EBV: about 95% of the cases in Central Africa, 40 to 50% of the cases in HIV-infected individuals and 10 to 20% of the sporadic cases harbour the viral information and express at least one viral antigen (EBNA1) and a number of non-coding viral RNAs. In contrast, all BL cases regardless of their geographical origin exhibit one of three c-myc/Ig chromosomal translocations leading to the activation of the c-myc gene as a crucial event in the development of this disease. Although epidemiological evidence clearly points to a role of the virus in the African cases, the role of EBV in the pathogenesis of BL has remained largely elusive. This review summarizes current concepts and ideas how EBV might contribute to the development of BL in the light of the progress made in the last decade and discusses the problems of the experimental systems available to test such hypotheses.

Interleukin-6 and Interleukin-10 Gene Promoter Polymorphisms and Risk of Endemic Burkitt Lymphoma

“…1,2 There are three subtypes of BL: endemic BL (eBL), which is Epstein Barr Virus (EBV) -positive, is the most common pediatric cancer in equatorial Africa, where Plasmodium falciparum malaria is holoendemic with an annual incidence of 5-15 cases in 100,000 children 3,4 ; sporadic BL (sBL), which is an order of magnitude less frequent than eBL, is associated with EBV in only approximately 15% of cases and diagnosed in developed countries at any age 5 ; and immune deficiency BL (idBL), which is also referred to as human immunodeficiency virus (HIV)-associated BL, occurs in adults who are immunecompromised as a result of HIV infection. 6 BL has the highest proliferative index of any known human cancer; it progresses rapidly, with the tumors doubling in size every 24-26 hours.…”

AIDS-related Burkitt lymphoma in the United States: what do age and CD4 lymphocyte patterns tell us about etiology and/or biology?

“…1 These clinical variants, which are defined in part by where they occur geographically, are histologically indistinguishable 1 and their etiology is incompletely understood. 2 eBL occurs in children mostly as extranodal jaw or orbital masses in equatorial Africa and Papua New Guinea. 3 sBL occurs anywhere in the world at any age mostly with abdominal or nodal involvement.…”

African Burkitt Lymphoma: Age-Specific Risk and Correlations with Malaria Biomarkers

“…6 However, EBV is not essential for aBL because most persons who are infected do not develop aBL, and it appears to play a less prominent role in sBL and AIDS-related BL because it is detected in at most 10 -20% and 30 -40% of cases, respectively. 8 African BL occurs in the context of Plasmodium falciparum malaria, which is presumed to be geographical co-factor of aBL, 9, 10 based on parallel distribution of both diseases. 10,11 The carriage of the sickle cell gene, a genetic marker for reduced risk of severe malaria, was significantly or marginally reduced in children with aBL 12 compared with hospital-based controls without aBL in two studies, 13,14 but not in the third study.…”