Hodgkin lymphoma is one of the most frequent haematological cancers and it forms an example of how medical research changes the prognosis of the illness. Some decades ago, this was regarded as a tumour with a poor clinical evolution in all diagnosed patients, and the arrival of new drugs turned it into a curable tumour in 85% of the cases. However, there is a 15% of Hodgkin lymphomas that do not respond to therapy and present a reduced survival.
Recently, the research group led by Manel Esteller, professor of Genetics at the UB, published an article in the journal Blood, which reveals a marker to predict which patients with Hodgkin lymphoma will present an aggressive clinical evolution and therefore, will be a case of high risk.
“We were studying genes that will chemically regulate a type of genetic material, RNA, and that would have lost its activity in cancer, and we found this was the case for ALKBH3”, notes Esteller. “Moreover –the researcher adds–, it was curious that its inactivity occurred only in a specific type of tumour: lymphomas, and specially in Hodgkin lymphoma”. By studying thousands of ARN molecules, researchers verified that the lack of the ALKBH3 expression in Hodgkin lymphoma induces an increase of the proteins called collagens, which constitute the extra-cell matrix where cancer cells live. That is, what happens in this case is that cancer cells change the microenvironment where they are in order to be comfortable and proliferate better. This subgroup of cases is the most malignant because cancer cells do not find barriers that stop their growth in the surrounding area. “It is important to know in advance which patients are in this group, since they are the perfect candidates to test new drugs, including epigenetic drugs that are used to treat other blood cancers, such as the myelodysplastic syndrome and the cutaneous lymphoma”, concludes Esteller, director of the Josep Carreras Leukaemia Research Institute (IJC), and ICREA research professor.
Esteve-Puig, R.; Climent, F.; Piñeyro, D.; Domingo-Domènech, E.; Dávalos, V.; Encuentra, M., Rea, A.; Espejo-Herrera, N.; Soler, M.; López, M.; Ortiz-Barahona, V.; Tapia, G.; Navarro, T.; Cid, J.; Farré, L.; Villanueva, A.; Casanova, I.; Mangues, R.; Santamarina-Ojeda, P.; Fernández, A. F.; Fraga, M. F.; Piris, M. A.; Kol, N.; Avrahami, C.; Moshitch-Moshkovitz, S.; Rechavi, G.; Sureda, A., and Esteller, M. “Epigenetic loss of m1A RNA demethylase ALKBH3 in Hodgkin lymphoma targets collagen conferring poor clinical outcome”. Blood, September 2020. Doi: 10.1182/blood.2020005823.