Burkitt Lymphoma

Burkitt lymphoma (BL) remains a prevalent pediatric cancer in sub-Saharan Africa and was the first human cancer identified with a virus when Epstein-Barr virus (EBV) was discovered in a Ugandan BL tumor in 1964. The impact of EBV in BL is highlighted by a new molecular tumor classification of EBV positivity versus negativity which is starting to supersede longstanding epidemiologic classifications. The high incidence of EBV-positive BL in Africa and Papua New Guinea has been linked to Plasmodium falciparum (Pf) malaria coinfections in young children. Epidemiologic studies have yielded insight into early-age EBV infections and have demonstrated direct impacts of Pf malaria infections on EBV reactivation and disruptions in EBV persistence. Moreover, when children residing in malaria holoendemic regions are contending with chronic Pf malaria infections, they undergo immune adaptations to mitigate life-threatening immunopathology. We postulate that this malaria-induced immune conditioning leads to diminished EBV-specific cellular immune surveillance, when combined with higher B cell proliferation, and EBV load creates a permissive environment for BL tumorigenesis.