Cancer causing mechanism found in children after malaria infection

New findings published in The Journal of Immunology have uncovered the role of Plasmodium falciparum (malaria) infection in the development of Burkitt’s lymphoma (BL), the most common childhood cancer in equatorial Africa and New Guinea. Since 1958, BL has been linked to malaria caused by P. falciparum, but the mechanism underlying how it leads to cancer has remained a mystery.

“Knowing that malaria plays a direct role in increasing cancer risk in children means that interventions to reduce the incidence of P. falciparum malaria in Africa may also reduce the incidence of Burkitt’s lymphoma,” shared Dr. Rosemary Rochford, Distinguished Professor of Immunology and Microbiology at the University of Colorado Anschutz School of Medicine, who led the study.

Burkitt’s lymphoma is a malignant disease of B cells, important cells in the immune system that produce antibodies. Although BL is a rare cancer worldwide, its incidence is 10 times higher in areas where malaria, caused by P. falciparum, is ever-present. Five Plasmodium species can cause malaria in humans, but only P. falciparum is associated with BL.

The study showed that in malaria due to P. falciparum infection in children, the expression of the enzyme AID (activation-induced cytidine deaminase) is significantly increased in B-cells. According to the researchers, this indicates a direct role of P. falciparum malaria in the development of BL due to the involvement of AID in the promotion of BL.

A hallmark of BL is the MYC gene translocation, a genetic mutation in which DNA breaks off from one chromosome and attaches to another. The enzyme AID is required for MYC translocation, so its presence in malaria patients confirms the role of P. falciparum malaria in the development of BL.

In this study, the blood of children with uncomplicated malaria was evaluated for AID levels and compared with the blood test results of children without malaria. Uncomplicated malaria is when a patient presents with nonspecific symptoms including fever, chills, sweating, headache, nausea and/or vomiting, without evidence of severe organ dysfunction.

AID levels were significantly elevated in B-cells from children with uncomplicated malaria and appeared to be fully functional. Functioning of excess AID also confirms the role of P. falciparum in causing BL.

Dr. Rochford hopes that “this study adds to the body of literature indicating the critical role of the AID enzyme in the etiology of Burkitt’s lymphoma and possibly other non-Hodgkin’s lymphomas.”

Dr. Rochford and her team are continuing this work by evaluating other effects of P. falciparum on immune function in children and how this creates a favorable environment for cancer development.