According to Dr. Sandrine Sander and Professor Klaus Rajewsky, Burkitt lymphoma originates from germinal centers of the lymphoid organs (Peyer's patches in the small intestine, spleen and lymph nodes). The reaction by the germinal center is triggered by the B cells when antigens are detected. Once the reaction occurs, the B cells alter their DNA causing a highly specific antibody response against the antigen.
The B cell receptor (BCR) plays a vital role in the reaction process. In order to fully recognize the antigen and trigger an appropriate immune response, the DNA segments encoding the antibody must be altered and rearranged. During this complicated process, DNA breaks may occur and error-prone repair mechanisms may result in genetic mutations linked with cancer development.
In Burkitt lymphoma, DNA repair errors lead to the translocation of the c-MYC oncogene, a gene that controls cell division. The c-MYC translocation causes affected cells to divide in an unregulated way and overexpression of the c-MYC results in massive cell death. As a result, c-MYC deregulation alone cannot convert normal cells into cancer cells. In Burkitt lymphoma, the apoptosis induction of elevated c-MYC expression must be overcome by additional mutations preventing cell death.
In a recent study, Professor Rejewsky and his team demonstrated the enzyme PI3K is vital for mature B cells to survive. PI3K stimulates a signaling pathway that controls cell growth and counteracts programmed cell death.
Dr. Sander and Professor Rajewsky based their current study on these findings. They examined the interaction of c-MYC and PI3K in mouse tumorigenesis. The team showed that PI3K is a vital component in the development of Burkitt lymphoma. They found that PI3K allows c-MYC to turn germinal center B lymphocytes into lymphoma cells that divide continuously and avoid apoptosis.
However, the researchers believe that other genetic mutations play a role in Burkitt lymphomagenesis as not every B cells co-expressing c-MYC and PI3K converts into a lymphoma cell. Such aberrations could be identified in their mouse model. In addition a study conducted by Professor Louis Staudt of the National Cancer Institute, Bethesda, Maryland, USA, showed that individuals suffering from Burkitt lymphoma, carry genetic mutations that resemble those in the mouse.
Dr. Sander and Professor Rajewsky explained:
"In addition to c-MYC deregulation, the activation of the PI3K signaling pathway is a key element in the development of Burkitt lymphoma. The inhibition of this signaling pathway could therefore be an effective strategy for treating the disease."