Scientists from the research center Applied Medicine (CIMA) of the University of Navarra have demonstrated the role of a protein in the correct assembly of the immune response and its implication in the development of an aggressive lymphoma subject . The results have been published in Bloodthe scientific journal of the American Society of Hematology and the one with the highest impact factor in the field of hematologic oncology.

FOXP1 protein expression is frequently deregulated in lymphomas, but little is known about its exact biological function or its role in lymphoma progression. "Therefore, we set out to delve into the functional relevance of this protein in B lymphocytes and to investigate its oncogenic role in the cell of origin of most lymphomas: the germinal center B cell," explain Drs. Sergio Roa, Ainara Sagardoy and José Ignacio Martínez-Ferrandis, researchers at CIMA and lead authors of work, directed by Dr. José A. Martínez-Climent.

To create an efficient immune response, B lymphocytes reorganize themselves in specialized microenvironments in germinal centers, located in the spleen and lymph nodes. "Our work confirms that FOXP1 is a factor core topic in the regulation of these processes and in the training germinal centers themselves. In addition, we have discovered that it is directly involved in the humoral immune response, regulating proliferation, differentiation and DNA repair processes that take place in germinal centers and that are frequently altered in the most aggressive lymphomas. Therefore, this protein may be a selective therapeutic target for a subgroup of B lymphomas that currently lacks curative treatment." Since more than half of B lymphomas arise from germinal center cells, the results could have an impact on the clinical management of the most common lymphoma, diffuse large cell lymphoma. These are preclinical molecular data that need to be further explored.

Researchers at CIMA have developed this work together with Dr. Ignacio Pérez Roger, from Cardenal Herrera-CEU University in Valencia. In addition, they have counted with the partnership of group of Professor Ari Melnick, from Cornell University in New York. "This project is part of a close scientific and technological partnership between the three centers".

Sixth most frequent cancer

B lymphomas represent the sixth most frequent cancer in developed countries. Despite being grouped as a single disease, they constitute a heterogeneous group of varied tumors that present different biological characteristics and different clinical evolution. "Currently, about 60% of patients with B lymphomas are cured with available treatments. However, some types of lymphomas, such as diffuse large B-cell lymphoma with activated phenotype, are resistant to current treatments, so new therapies are needed. Our group seeks to identify the proteins core topic for tumor survival in these aggressive lymphomas, with the aim of developing drugs that can selectively eliminate these tumor cells. We think that FOXP1 could be one of these target proteins for diffuse large cell lymphoma, which represents about 35-40% of all B-cell lymphomas", explain Drs. Sagardoy, Martínez-Ferrandis and Roa.