engleski

Histone modification H3K27me3 in MALT lymphoma is dependent on amount of FOXP3 cells infiltrating tumor mass

Extranodal marginal zone lymphoma of MALT (mucosa-associated lymphoid tissue) type is a low-grade B-cell lymphoma that originates from mature B-cells. Those cells are believed to be marginal zone cells of secondary follicles, which are generated in response to various types of chronic inflammations. Gastric MALT lymphoma is the most common MATL lymphoma and is often associated with infection of Helicobacter pylori. Genetic events in MALT lymphoma (t(11 ; 18)(q21 ; q21), t(1 ; 14)(p22 ; q32), t(14 ; 18)(q32 ; q21) and t(3 ; 14)(p14.1 ; q32) as well as trisomies 3 and 18) are well defined, deregulation of protein function as a result of different translocations are well described and the evidence that MALT lymphoma is an antigen driven neoplasm are already existing. Epigenetic alterations that could lead to new therapeutic strategies are, on the other hand, not sufficiently studied. At the DNA level, an increased methylation of specific genes (p16, MGMT and MINT31) in relation to H. pylori infection was found, while histone methylation marks were suggested to play an important role in altering gene expression in all hematological malignancies. The important aspect of epigenetic marks is that they can be modified by microenvironmental signals such as the interaction of FOXP3 T regulatory (Treg) cells with tumor B cells. In this case study we have investigated the presence of the histone modification H3K27me3 in tumor cells of gastric MALT lymphoma in relation to the amount of FOXP3 regulatory cells, which infiltrate the tumor mass. Samples from the gastric biopsies performed at the time of diagnosis, as well as after each cycle of therapy, were analyzed. Regardless of the treatment protocol used and different disease development in each patient, all of the cases exhibit one unique property – depending on the severity of disease, the amount of FOXP3 cells varies and is inversely correlated to the proportion of tumor cells that highly express H3K27me3. These data suggest that FOXP3 cells potentially affect tumor B-cells in a way to initiate a pathway that results in decreased amounts of tumor cells expressing the histone modification H3K27me3. Since H3K27me3 is associated with transcriptional repression of many genes during normal development, stem cell maintenance and differentiation, our findings indicate strong recruitment of T regs during tumor development to facilitate its further growth by reactivation of certain developmentally regulated genes. Such data could serve as a basis for new therapy protocols aiming to interfere with the described cell communication.

H3K27me3; FOXP3; MALT lymphoma

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