title: Natural killer cells in patients with polycythemia vera.
abstract: Natural killer cells (NK) are pivotal cells of innate immunity. They are potent antileukemic cytotoxic effectors. A defect in their cytotoxicity has been described in some hematopoietic malignancies such as acute myeloid leukemia, multiple myeloma and myelodysplastic syndromes. This defect is at least partially linked to a decreased or absent expression of some activating NK cells molecules, more particularly the so-called natural cytotoxicity receptors. In the present study, we more particularly focused our attention on NK cells of polycythemia vera, a myeloproliferative disease characterized by the presence of mutated JAK2 tyrosine kinase. The polymerase chain reaction analysis of NK cells from patients showed that they expressed the mutated form of JAK2. In polycythemia vera the proportion of NK was increased compared to healthy donors. The proliferative and cytotoxic abilities of NK cells from patients were similar to healthy donors. Expression of activating or inhibitory receptors was comparable in patients and donors, with nonetheless an imbalance for the inhibitory form of the CD158a,h couple of receptors in patients. Finally, the transcriptomic profile analysis clearly identified a discriminant signature between NK cells from patients and donors that could putatively be the consequence of abnormal continuous activation of mutated JAK2.
authors.affiliation: Aix-Marseille Université, UMR 1090 TAGC, Marseille, France; AP-HM, Hôpital de La Conception, Service d'Hématologie et Thérapie Cellulaire, Marseille, France; AP-HM, Laboratoire d'Hématologie, Hôpital Nord, Marseille, France; Laboratoire de Biologie Médicale, Centre Hospitalier, Salon de Provence, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Sanchez
authors.affiliation: Aix-Marseille Université, UMR 1090 TAGC, Marseille, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Baier
authors.affiliation: Aix-Marseille Université, UMR 1090 TAGC, Marseille, France; AP-HM, Hôpital de La Conception, Service d'Hématologie et Thérapie Cellulaire, Marseille, France.
authors.forename: Julien G
authors.initials: JG
authors.lastname: Colle
authors.affiliation: Aix-Marseille Université, UMR 1090 TAGC, Marseille, France.
authors.forename: Rabie
authors.initials: R
authors.lastname: Chelbi
authors.affiliation: Aix-Marseille Université, UMR 1090 TAGC, Marseille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Rihet
authors.affiliation: AP-HM, Laboratoire d'Hématologie, Hôpital Nord, Marseille, France.
authors.forename: Thérèse
authors.initials: T
authors.lastname: Le Treut
authors.affiliation: Aix-Marseille Université, UMR 1090 TAGC, Marseille, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Imbert
authors.affiliation: AP-HM, Hôpital de La Conception, Service d'Hématologie et Thérapie Cellulaire, Marseille, France; AP-HM, Laboratoire d'Hématologie, Hôpital Nord, Marseille, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Sébahoun
authors.affiliation: Aix-Marseille Université, UMR 1090 TAGC, Marseille, France; AP-HM, Hôpital de La Conception, Service d'Hématologie et Thérapie Cellulaire, Marseille, France.
authors.forename: Geoffroy
authors.initials: G
authors.lastname: Venton
authors.affiliation: Aix-Marseille Université, UMR 1090 TAGC, Marseille, France; AP-HM, Hôpital de La Conception, Service d'Hématologie et Thérapie Cellulaire, Marseille, France; AP-HM, Laboratoire d'Hématologie, Hôpital Nord, Marseille, France. Electronic address: regis.costello@free.fr.
authors.forename: Régis T
authors.initials: RT
authors.lastname: Costello
mesh_terms: D000368:Aged; D000954:Antigens, Surface / Q000378:metabolism; D016022:Case-Control Studies; D016000:Cluster Analysis; D003602:Cytotoxicity, Immunologic; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D016130:Immunophenotyping; D053614:Janus Kinase 2 / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011087:Polycythemia Vera / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D055607:Receptors, Natural Killer Cell / Q000235:genetics / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D055607:Receptors, Natural Killer Cell; D053614:Janus Kinase 2
keywords: Cytotoxicity; Expansion; Natural cytotoxicity receptors; Natural killer; Transcriptome analysis