Burkitt lymphoma, a cancer that impacts a subset of immune cells called B cells, develops most often in children and young adults. Patients with Burkitt lymphoma exhibit elevated levels of a protein called activation-induced cytidine deaminase (AID), which acts as an enzyme to accelerate a genetic process known as “translocation.” In cases of Burkitt lymphoma, AID promotes translocation of MYC, a gene that codes for cellular functions like growth, maturation, and death.
Certain viral and parasitic diseases can play a role in causing various types of cancer. Studies have shown that both Epstein-Barr virus (EBV), the virus that causes mononucleosis, and Plasmodium falciparum (P. falciparum), the parasite that causes malaria, relate to Burkitt lymphoma incidence. However, scientists don’t fully understand how either of these pathogens drives the development of Burkitt lymphoma.
To address the pathogenesis of Burkitt lymphoma related to EBV and P. falciparum, a team of researchers evaluated how each pathogen impacted AID expression. The researcher recently published their findings in the Journal of Immunology.
The researchers obtained blood samples from children with a malaria infection treated at a hospital in Kenya. Age-matched children in the community who didn’t exhibit any malaria symptoms provided control samples. Blood samples contain peripheral blood mononuclear cells (PBMCs), including immune cells like B and T cells.
The research team performed flow cytometry on the PBMCs. This laboratory technique uses fluorescent tagging to evaluate specific markers found on the surface or inside cells, providing a reliable way to identify and quantify cells expressing AID and CD19. The analysis revealed that children with malaria had elevated numbers of B cells expressing AID and another marker related to lymphoma, CD19, compared to controls. Elevated AID persisted for up to eight weeks after patients cleared the P. falciparum parasite. The study also found that about half of the AID in PBMCs of children with malaria is localized to the nucleus of CD19-expressing B cells.
To determine if EBV could further drive AID expression in patients with P. falciparum infection, the researchers used laboratory approaches to evaluate synergy, a condition in which the combination of two effects exceeds the effect of either single component. In this context, it means that the combined effect of EBV and the agent that mimics the DNA of P. falciparum on AID expression is greater than the sum of their individual effects. This experiment involved stimulating CD19-expressing B cells with EBV with or without an agent that mimics the DNA of P. falciparum. The combination treatment induced about 30% more cells expressing both CD19 and AID than the monotherapies.
The authors conclude that children infected with malaria express sustained AID levels in B cells. The demonstration that coinfection of P. falciparum and EBV synergized to impact AID expression provides, for the first time, a mechanistic link between malaria and Burkitt lymphoma. These data support the concept that P. falciparum could serve as a cancer-causing parasite, a finding that raises intriguing questions about the potential implications for cancer treatment, particularly in regions with high rates of malaria infection.
Sources: J Immunol
