EPIGENETIC CHANGES IN MALT LYMPHOMA AND THE ACCUMULATION OF FOXP3+ REGULATORY CELLS IN TUMOR MASS

Eva Lovric; Tomislav Horvat; Miroslava Katicic; Slobodanka Ostojic Kolonic; Slavko Gasparov; Vlatka Zoldos; Petra Korac; Mara Dominis

Eva Lovric Institute of Pathology and Cytology, University Hospital Merkur
Tomislav Horvat Faculty of Science, Division of Molecular Biology, Department of Biology, University of Zagreb
Miroslava Katicic Medical School, University of Zagreb
Slobodanka Ostojic Kolonic Medical School, University of Zagreb; Department of Medicine, University Hospital Merkur
Slavko Gasparov Institute of Pathology and Cytology, University Hospital Merkur; Medical School, University of Zagreb
Vlatka Zoldos Faculty of Science, Division of Molecular Biology, Department of Biology, University of Zagreb
Petra Korac Faculty of Science, Division of Molecular Biology, Department of Biology, University of Zagreb
Mara Dominis Medical School, University of Zagreb

Keywords: API2/MALT1, FOXP3, H3K27me3, MALT lymphoma

Abstract

Primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is often induced by a chronic Helicobacter pylori infection, while a significant role during its development is ascribed to T lymphocytes, which infiltrate the tumor mass. Even though it is well known that FOXP3+ T regulatory cells can modify clinical outcome of hematological malignancies, it is still unknown whether they can induce epigenetic changes in lymphoma cells. Using gastric biopsies from 11 patients with MALT lymphoma at the time of diagnosis, during follow-up and during progression of the disease, we have analyzed 138 biopsies in total in order to assess the possible association of changes in H3K27me3 production and the presence of cytogenetic changes in small lymphocytes, with the presence of FOXP3+ cells that infiltrate tumor tissue. Our results indicate a putative role of FOXP3+ cells in mechanisms leading to a decreased expression of repressive histone modification H3K27me3 in tumor cells, which could result in transcriptional reactivation of various genes associated with tumor growth and disruption of genomic integrity characteristic of tumor cells.