Epigenetics predicts the aggressiveness of Burkitt lymphoma, a common pediatric tumor in developing countries microbiologystudy

Research into the most prevalent tumors in developing countries significantly lags behind research into those cancers that are more common in Western countries, resulting in higher mortality rates. One such example is Burkitt lymphoma, the most frequent tumor among the pediatric population in Equatorial Africa and in certain regions of the Pacific and South America.

In these areas, the disease is considered endemic and is largely associated with infection by the Epstein-Barr virus (EBV). In contrast, in other parts of the world it is classified as “sporadic” and typically arises in individuals with compromised immune systems, such as those living with human immunodeficiency virus (HIV).

With the aim of improving our understanding of Burkitt lymphoma, a team co-led by Dr. Manel Esteller, ICREA Research Professor at the Josep Carreras Leukemia Research Institute (IJC) and Chair of Genetics at the Faculty of Medicine, University of Barcelona, together with Dr. Ryan Morin from Canada’s Michael Smith Genome Sciences Center, BC Cancer, in Vancouver (Canada), has revealed that the epigenome enables classification of the disease’s aggressiveness and biological characteristics.

The findings are published in Blood Cancer Discovery.

To this end, the researchers analyzed the epigenetic profiles of over 200 Burkitt lymphoma samples, collected from four continents and including both pediatric and adult cases.

By studying the patients’ DNA methylation, they discovered that the epigenome divides these tumors into two distinct types, named HypoBL and HyperBL.

According to Dr. Esteller, “The first is characterized by relatively few epigenetic defects in the tumor cells and their composition makes them more similar to healthy B lymphocytes. Individuals with this ‘epitype’ tend to have a relatively favorable clinical course.”

The second group, however, is characterized by a much higher degree of DNA methylation in the affected cells, a process known as hypermethylation, which leads to the silencing of hundreds of genes, many related to tumor suppression.

Moreover, these cases often exhibit a high load of Epstein-Barr virus, an external factor that may contribute to the epigenetic “malignization” of the cells. Epigenetically, these cells share few similarities with healthy B cells and show clear signs of cellular transformation.

“All of these factors mean that patients in the HyperBL Burkitt lymphoma group tend to relapse earlier and have shorter survival,” explains Dr. Esteller, adding that “having this information from the time of diagnosis should prompt us to reconsider the most appropriate treatment strategy, based on the clinical severity of the disease.”

In this way, thanks to these new insights into Burkitt lymphoma, tumors with a better prognosis could continue to receive standard chemotherapy, while more aggressive cases might be considered for clinical trials of novel drugs or for specific forms of immunotherapy.