Researchers may have uncovered the role of Plasmodium falciparum malaria in the development of Burkitt lymphoma, according to a recent study published by Ariera et al in The Journal of Immunology.
Background
Uncomplicated malaria occurs when a patient’s symptoms are nonspecific, including fever, chills, sweating, headache, nausea, and/or vomiting without signs of severe organ dysfunction.
Burkitt lymphoma—the most common cancer type among pediatric patients in equatorial Africa and New Guinea—affects B cells. While the disease is rare globally, its prevalence is 10 times higher in regions with a consistent presence of P falciparum malaria. Five different species of Plasmodium can cause malaria in humans, but only P falciparum is associated with Burkitt lymphoma. Although the disease has been associated with P falciparum malaria since 1958, little is known about the underlying mechanisms leading to cancer.
“Knowing that malaria has a direct role in increasing [the] cancer risk [among pediatric patients] means that measures to reduce the burden of P falciparum malaria in Africa could also reduce the incidence of Burkitt lymphoma,” highlighted senior study author Rosemary Rochford, PhD, Distinguished Professor of Immunology and Microbiology at the University of Colorado Anschutz School of Medicine.
Study Methods and Results
Researchers assessed blood samples from pediatric patients with uncomplicated malaria and those without malaria for levels of the activation-induced cytidine deaminase (AID) enzyme.
The researchers found an elevated expression of the AID enzyme in the B cells of the pediatric patients with uncomplicated P falciparum malaria. They detailed that a hallmark of Burkitt lymphoma is the translocation of the MYC gene, a genetic mutation in which DNA breaks off one chromosome and attaches to another. The AID enzyme is essential for MYC translocation, which is why its presence in patients with malaria indicated P falciparum malaria’s direct involvement in the development of Burkitt lymphoma.
Further, the AID enzyme was found to be fully functional. The functionality of the excess AID enzyme also supported the role of P falciparum in causing Burkitt lymphoma.
“[T]his study adds to the body of literature pointing to a critical role of the enzyme, AID, in the etiology of Burkitt lymphoma and potentially in other non-Hodgkin lymphomas,” Dr. Rochford underscored.
The researchers are currently evaluating the other effects of P falciparum on immune function in pediatric patients to determine how the disease creates a permissive environment for cancer.
Disclosure: For full disclosures of the study authors, visit academic.oup.com.
