Effects of 5-azacytidine on natural killer cell activating receptor expression in patients with refractory anemia with excess of blasts. Issue 1 (2015)

• Record Type: Journal Article
• Authors: Costello, Régis T.; Leclercq, Amélie; Treut, Thérèse Le; Sanchez, Carole; Mercier, Delphine; Sébahoun, Gérard
• Is Part Of: Leukemia research reports. Volume 4:Issue 1(2015)
• Page Start: 15
• Page End: 17
• Publication Date: 2015
• Subjects: Natural killer cells -- Refractory anemia with excess of blasts -- Natural cytotoxicity receptors -- Demethylation -- 5-azacytidine; Leukemia -- Periodicals; Lymphomas -- Periodicals; Multiple myeloma -- Periodicals; Leukemia -- Periodicals; Lymphoma -- Periodicals; Multiple Myeloma -- Periodicals; Hematologic Neoplasms -- Periodicals; Leukemia; Lymphomas; Multiple myeloma; Electronic journals; Periodicals; 616.9941905
• DOI: 10.1016/j.lrr.2014.09.004
• Languages: English
• ISSNs: 2213-0489

Abstract

Abstract: 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.