title: Effects of 5-azacytidine on natural killer cell activating receptor expression in patients with refractory anemia with excess of blasts.
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.
authors.affiliation: Laboratoire d'Hématologie, Hôpital Nord, Marseille, France ; Université de la Méditerranée, France ; Technologies Avancées pour la Génomique et la Clinique (TAGC)/unité INSERM U1090, Route de Luminy, Marseille, France ; Service d'Hématologie et Thérapie Cellulaire, Centre Hospitalier Universitaire La Conception, 147 Boulevard Baille, 13005 Marseille, France.
authors.forename: Régis T
authors.initials: RT
authors.lastname: Costello
authors.affiliation: Laboratoire d'Hématologie, Hôpital Nord, Marseille, France ; Université de la Méditerranée, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Leclercq
authors.affiliation: Laboratoire d'Hématologie, Hôpital Nord, Marseille, France ; Université de la Méditerranée, France.
authors.forename: Thérèse Le
authors.initials: TL
authors.lastname: Treut
authors.affiliation: Laboratoire d'Hématologie, Hôpital Nord, Marseille, France ; Université de la Méditerranée, France ; Technologies Avancées pour la Génomique et la Clinique (TAGC)/unité INSERM U1090, Route de Luminy, Marseille, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Sanchez
authors.affiliation: Laboratoire d'Hématologie, Hôpital Nord, Marseille, France ; Université de la Méditerranée, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Mercier
authors.affiliation: Laboratoire d'Hématologie, Hôpital Nord, Marseille, France ; Université de la Méditerranée, France ; Service d'Hématologie et Thérapie Cellulaire, Centre Hospitalier Universitaire La Conception, 147 Boulevard Baille, 13005 Marseille, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Sébahoun
keywords: 5-azacytidine; Demethylation; Natural cytotoxicity receptors; Natural killer cells; Refractory anemia with excess of blasts