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

Research into the most prevalent tumours in developing countries significantly lags behind research into those cancers that are more in Western countries, resulting in higher mortality rates. One such example is Burkitt lymphoma, the most frequent tumour among the paediatric 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 Leukaemia Research Institute (IJC) and Chair of Genetics at the Faculty of Medicine, University of Barcelona, together with Dr Ryan Morin from the Canada’s Michael Smith Genome Sciences Centre, BC Cancer, in Vancouver (Canada), has revealed that the epigenome enables to classify the disease’s aggressiveness and biological characteristics. The findings have recently been published in Blood Cancer Discovery, the official journal of the American Association for Cancer Research (AACR).

To this end, the researchers analysed the epigenetic profiles of over 200 Burkitt lymphoma samples, collected from four continents and including both paediatric and adult cases. By studying the patients’ DNA methylation, they discovered that the epigenome divides these tumours into two distinct types, named HypoBL and HyperBL. According to Dr Esteller, “the first is characterised by relatively few epigenetic defects in the tumour cells and their composition makes them more similar to healthy B lymphocytes. Individuals with this ‘epitype’ tend to have a relatively favourable clinical course.”

The second group, however, is characterised 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 with tumour suppression. Moreover, these cases often exhibit a high load of Epstein-Barr virus, an external factor that may contribute to the epigenetic ‘malignisation’ 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, tumours 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.

This research has been partially funded by the Foundation for Burkitt Lymphoma Research, the National Cancer Institute (USA), the National Institutes of Health (USA), the Spanish Ministry of Science, Innovation and Universities, and the Government of Catalonia.

Reference Article: Thomas N, García-Prieto C, Dreval K, Hilton L, Abramson J, Bartlett N, Bethony J, Bowen J, Bryan A, Casper C, Dyer M, Gastier-Foster J, Gerrie A, Greiner T, Griner N, Gross T, Harris N, Irvin J, Jaffe E, Leal F, Mbulaiteye S, Mullighan C, Mungall A, Mungall K, Namirembe C, Noy A, Ogwang M, Orem J, Ott G, Petrello H, Reynolds S, Swerdlow S, Traverse-Glehen A, Wilson W, Marra M, Staudt L, Scott D, Esteller M*, Morin R*. DNA methylation epitypes of Burkitt lymphoma with distinct molecular and clinical features. Blood Cancer Discovery, DOI: 10.1158/2643-3230.BCD-24-0240, 2025.