Epigenetic regulation of BCL6 in B-cell lymphoma : effects of romidepsin, a histone deacetylase inhibitor

Abstract

BCL6 is a transcriptional repressor essential for germinal centre formation and regulation of lymphocyte function, differentiation and survival. The deregulation in the expression of this gene is associated with the development of B-cell lymphomas. This deregulation is frequently caused by genetic modifications like translocations or point mutations and recently it has been demonstrated that epigenetic mechanisms are also involved. Histone deacetylases (HDAC) are important targets for epigenetic treatment in cancer cells. Romidepsin is a HDAC inhibitor used in cutaneous T-cell lymphoma treatment but possible effects in B-cells lymphoma are not known in detail. In the present study, we analyzed the effects of Romidepsin on the proliferation, differentiation and death of different human B-cell lymphoma cells lines as well as its effects on BCL6 expression. Cytotoxic effect of Romidepsin was found in some cells lines, while others were resistant to high doses of Romidepsin. Depending on the cell line, treatment with this drug induces cell cycle arrest in G0/G1 phase, apoptosis and/or differentiation to plasma cells. Interestingly, these effects were accompanied with increased expression of cell cycle inhibitors and BCL6 mRNA and protein downregulation.