Effects of 5-azacytidine on natural killer cell activating receptor expression in patients with refractory anemia with excess of blasts

摘要

Epigenetic drugs modify DNA methylation and are used in refractory anemia with excess of blasts (RAEB). These drugs may reactivate anti-oncogene expression and restore a normal phenotype instead of inducing antitumor toxicity, although they also have immunosuppressive effects on T-lymphocytes [1] In RAEB and acute myeloid leukemia, a defect in natural killer (NK) cell cytotoxicity has been shown, which relies on abnormal expression of activating receptors. Previous study has shown that 5-azacytidine impaired mRNA synthesis and induced apoptosis in NK cells [2]. In this study we investigated the effect of the demethylating drug 5-azacytidine (Vidaza ? ) on NK receptors with the hypothesis that demethylation of the promoters of activating NK receptor genes induces gene reactivation and thus may increase their expression. Highlights ? We analyze the effects of the demethylating agent azacytidine on NK cells in RAEB. ? The expression of NCRs and NKG2D activating molecules are not modified. ? The expression of the co-stimulating molecule 2B4/CD244 is drastically decreased. ? The expression of inhibitory NK cell molecules is not modified (data not shown). ? These data argue for the association of demethylating agents with IMIDs in RAEB.