Hypomethylation of the promoter region drives ectopic expression of TMEM244 in Sézary cells.

Sezary syndrome (SS) is an aggressive form of cutaneous T-cell lymphoma (CTCL) characterized by the presence of circulating malignant CD4+ T cells (Sezary 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 geneTMEM244is 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 linesTMEM244expression is negatively correlated with the methylation level of its promoter. Furthermore, we demonstrate thatTMEM244expression can be activated in vitro by the CRISPR-dCas9-induced specific demethylation ofTMEM244promoter region. Since both,TMEM244expression and its promoter demethylation, are not detected in normal lymphoid cells, they can be potentially used as markers in Sezary syndrome and some other T-cell lymphomas.