title: Overexpression of CD158 and NKG2A Inhibitory Receptors and Underexpression of NKG2D and NKp46 Activating Receptors on NK Cells in Acute Myeloid Leukemia.
abstract: OBJECTIVE
  Natural killer (NK) cells are innate immune system cells that are actively involved in immune-surveillance of tumor cells. Recognition of tumors by NK cells occurred via natural cytotoxicity receptors and killer cell immunoglobulin-like receptors. Some ligands of the activating receptors seem to be present on malignant cells from patients with acute myeloid leukemia. The aim of the study was to evaluate the expression of activating receptors such as NKG2D, DNAM-1, NKp30, and NKp46, and inhibitory receptors such as NKG2A, CD158b, CD158a, and CD158e1 on NK cells from patients with newly diagnosed acute myeloid leukemia before and after stimulation with IL-2 and IL-12.
  
  
  METHODS
  Patients were divided into two groups: group 1 AML M3, and group 2 non-M3 AML. Flow cytometry was performed on whole PBMC to evaluate NK cell receptors.
  
  
  RESULTS
  Twenty one AML patients, aged 26-78 years, and 11 matched healthy individuals were studied. NKG2D, and NKp46 expression was decreased in group 1 (p <0.019). Patients in Group 2 showed underexpression of the activating receptors NKp46. Differences after stimulation of NK cells with IL-2 and IL-12 were observed only in Group 2, in which a significant decrease in the expression of NKp46 receptor was found (p <0.0016). Patients in groups 1 and 2 showed overexpression of the inhibitory receptors CD158b (p <0.007) and NKG2A (p <0.01).
  
  
  CONCLUSIONS
  NKG2D receptor expression is decreased in patients with AML M3. In addition, patients with all FAB types of AML have overexpression of inhibitory receptors such as CD158b and NKG2A and decreased expression of the activating receptor NKp46.
authors.affiliation: Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México, México.
authors.forename: Daniela
authors.initials: D
authors.lastname: Sandoval-Borrego
authors.affiliation: Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México, México.
authors.forename: Martha C
authors.initials: MC
authors.lastname: Moreno-Lafont
authors.affiliation: Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México, México.
authors.forename: Ernesto Antonio
authors.initials: EA
authors.lastname: Vazquez-Sanchez
authors.affiliation: Cátedra CONACYT, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Ciudad de México, México.
authors.forename: Adriana
authors.initials: A
authors.lastname: Gutierrez-Hoya
authors.affiliation: Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México, México.
authors.forename: Rubén
authors.initials: R
authors.lastname: López-Santiago
authors.affiliation: Unidad Médica de Alta Especialidad, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Ciudad de México, México; Departamento de Morfología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México, México.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Montiel-Cervantes
authors.affiliation: Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México, México.
authors.forename: Maricela
authors.initials: M
authors.lastname: Ramírez-Saldaña
authors.affiliation: Unidad Médica de Alta Especialidad, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Ciudad de México, México; Departamento de Morfología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México, México. Electronic address: velaj12x@prodigy.net.mx.
authors.forename: Jorge
authors.initials: J
authors.lastname: Vela-Ojeda
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000378:metabolism; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000378:metabolism; D055607:Receptors, Natural Killer Cell / Q000032:analysis / Q000276:immunology / Q000378:metabolism*
chemical_list: D007376:Interleukin-2; D055654:NK Cell Lectin-Like Receptor Subfamily C; D055655:NK Cell Lectin-Like Receptor Subfamily K; D055627:Natural Cytotoxicity Triggering Receptor 1; D055607:Receptors, Natural Killer Cell; D018664:Interleukin-12
keywords: Acute myeloid leukemia (AML); Killer cell immunoglobulin-like receptors (KIRs); NK cell receptors; NK cells; Natural cytotoxicity receptors (NCRs)