Hypomethylation of the promoter region drives ectopic expression of TMEM244 in Sézary cells. Issue 18 (14th August 2020) - Iżykowska, Katarzyna
Abstract: Sézary syndrome (SS) is an aggressive form of cutaneous T‐cell lymphoma (CTCL) characterized by the presence of circulating malignant CD4+ T cells (Sézary cells) with many complex changes in the genome, transcriptome and epigenome. Epigenetic dysregulation seems to have an important role in the development and progression of SS as it was shown that SS cells are characterized by widespread changes in DNA methylation. In this study, we show that the transmembrane protein coding gene TMEM244 is ectopically expressed in all SS patients and SS‐derived cell lines and, to a lower extent, in mycosis fungoides and in a fraction of T‐cell lymphomas, but not in B‐cell malignancies and mononuclear cells of healthy individuals. We show that in patient samples and in the T‐cell lines TMEM244 expression is negatively correlated with the methylation level of its promoter. Furthermore, we demonstrate that TMEM244 expression can be activated in vitro by the CRISPR‐dCas9–induced specific demethylation of TMEM244 promoter region. Since both, TMEM244 expression and its promoter demethylation, are not detected in normal lymphoid cells, they can be potentially used as markers in Sézary syndrome and some other T‐cell lymphomas.