Malaria - how this parasitic infection aids and abets EBV-associated Burkitt lymphomagenesis.
Burkitt lymphoma (BL) is >90% EBV-associated when this pediatric cancer is diagnosed in regions heavily burden by endemic Plasmodium falciparum malaria and thus has been geographically classified as endemic BL. The incidence of endemic BL is 10-fold higher compared to BL diagnosed in non-malarious regions of the world. The other forms of BL have been classified as sporadic BL which contain EBV in ∼30% of cases and immunodeficiency BL which occurs in HIV-infected adults with ∼40% of tumors containing EBV. Within malaria endemic regions, epidemiologic studies replicating Denis Burkitt's seminal observation continue to show differences in endemic BL incidence linked to intensity of malaria transmission. However, the mechanisms by which malaria contributes to B cell tumorigenesis have not been resolved to the point of designing cancer prevention strategies. The focus of this review is to summarize our current knowledge regarding the influence of prolonged, chronic malaria exposure on defects in immunosurveillance that would otherwise control persistent EBV infections. And thus, set the stage for ensuing mechanisms by which malaria could instigate B cell activation and aberrant activation-induced cytidine deaminase expression initiating somatic hypermutation and thereby increasing the likelihood of an Ig/Myc translocation, the hallmark of all BL tumors. Malaria appears to play multiple, sequential and simultaneous roles in endemic BL etiology; the complexity of these interactions are being revealed by applying computational methods to human immunology. Remaining questions yet to be addressed and prevention strategies will also be discussed.
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA. Electronic address: ann.moormann@umassmed.edu.
Ann M
AM
Moormann
Program for Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA, USA.
Jeffrey A
JA
Bailey
D002051:Burkitt Lymphoma / Q000453:epidemiology* / Q000503:physiopathology*; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D006801:Humans; D015994:Incidence; D016778:Malaria, Falciparum / Q000150:complications*; D010963:Plasmodium falciparum / Q000472:pathogenicity*
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