Functional characterization of NK cells in Mexican pediatric patients with acute lymphoblastic leukemia: Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia


Autoři: Lucero Valenzuela-Vazquez aff001;  Juan Carlos Núñez-Enríquez aff002;  Jacqueline Sánchez-Herrera aff001;  Elva Jiménez-Hernández aff003;  Jorge Alfonso Martín-Trejo aff004;  Laura Eugenia Espinoza-Hernández aff003;  Aurora Medina-Sanson aff005;  Luz Victoria Flores-Villegas aff006;  José Gabriel Peñaloza-González aff007;  José Refugio Torres-Nava aff008;  Rosa Martha Espinosa-Elizondo aff009;  Raquel Amador-Sánchez aff010;  Jessica Denisse Santillán-Juárez aff011;  Janet Flores-Lujano aff002;  María Luisa Pérez-Saldívar aff002;  Luis Ramiro García-López aff012;  Alejandro Castañeda-Echevarría aff013;  Francisco Rodríguez-Leyva aff014;  Haydeé Rosas-Vargas aff015;  Minerva Mata-Rocha aff015;  David Aldebarán Duarte-Rodríguez aff002;  Omar Alejandro Sepúlveda-Robles aff015;  Ismael Mancilla-Herrera aff016;  Juan Manuel Mejía-Aranguré aff017;  Mario Ernesto Cruz-Munoz aff001
Působiště autorů: Facultad de Medicina, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, Mexico aff001;  Unidad de Investigación Médica en Epidemiología Clínica, UMAE Hospital de Pediatría, Centro Médico Nacional (CMN) "Siglo XXI", Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico aff002;  Servicio de Hematología Pediátrica, Hospital General “Gaudencio González Garza”, Centro Médico Nacional (CMN) "La Raza", IMSS, Mexico City, Mexico aff003;  Servicio de Hematología Pediátrica, UMAE Hospital de Pediatría, Centro Médico Nacional (CMN) "Siglo XXI", Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico aff004;  Servicio de Hemato-Oncologia, Hospital Infantil de México Federico Gómez, Secretaria de Salud (SS), Mexico City, Mexico aff005;  Servicio de Hematología Pediátrica, Centro Médico Nacional (CMN) “20 de Noviembre”, Instituto de Seguridad Social al Servicio de los Trabajadores del Estado (ISSSTE), Mexico City, Mexico aff006;  Servicio de Onco-Pediatria, Hospital Juárez de México, Secretaria de Salud (SS), Mexico City, Mexico aff007;  Servicio de Oncología, Hospital Pediátrico de Moctezuma, Secretaría de Salud del D.F., Mexico City, Mexico aff008;  Servicio de Hematología Pediátrica, Hospital General de México, Secretaria de Salud (SS), Mexico City, Mexico aff009;  Hospital General Regional No. 1 "Carlos McGregor Sánchez Navarro", IMSS, Mexico City, Mexico aff010;  Servicio de Hemato-oncología Pediátrica, Hospital Regional No. 1° de Octubre, ISSSTE, Mexico City, Mexico aff011;  Servicio de Pediatría, Hospital Pediátrico de Tacubaya, Secretaría de Salud (SS), Mexico City, Mexico aff012;  Servicio de Pediatría, HGR No. 25, IMSS, Mexico City, Mexico aff013;  Servicio de Cirugía Pediátrica, HGZ No. 30 IMSS, Mexico City, Mexico aff014;  Unidad de Investigación Médica en Genética Humana, UMAE Hospital de Pediatría, Centro Médico Nacional (CMN) "Siglo XXI", IMSS, Mexico City, Mexico aff015;  Departamento de infectología e inmunología, Instituto Nacional de Perinatología, Mexico City, Mexico aff016;  Coordinación de Investigación en Salud, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico aff017
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227314

Souhrn

Acute lymphoblastic leukemia (ALL) is the most common cancer in children around the globe. Mexico City has one of the highest incidence rates of childhood leukemia worldwide with 49.5 cases per million children under the age of 15 which is similar to that reported for Hispanic populations living in the United States. In addition, it has been noted a dismal prognosis in Mexican and Hispanic ALL pediatric population. Although ALL, like cancer in general, has its origins in endogenous, exogenous, and genetic factors, several studies have shown that the immune system also plays a deterministic role in cancer development. Among various elements of the immune system, T lymphocytes and NK cells seem to dominate the immune response against leukemia. The aim of the present study was to perform a phenotypic and functional characterization of NK cells in ALL Mexican children at the moment of diagnosis and before treatment initiation. A case-control study was conducted by the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia (MIGICCL). 41 cases were incident ALL children younger than 17 years old and residents of Mexico City. 14 controls were children without leukemia, matched by age and sex with cases. NK cell function was evaluated by degranulation assays towards K562 cells and SLAM-associated protein (SAP) expression was measured by intracellular staining. All assays were performed using peripheral blood mononuclear cells from controls and patients. The results indicate that NK mediated cytotoxicity, measured by CD107a degranulation assays in response to K562 cells, was reduced in ALL patients compared to controls. Interestingly, an impaired NK cell killing of target cells was not equally distributed among ALL patients. In contrast to patients classified as high-risk, standard-risk patients did not display a significant reduction in NK cell-mediated cytotoxicity. Moreover, patients presenting a leukocyte count ≥ 50,000xmm3 displayed a reduction in NK-cell mediated cytotoxicity and a reduction in SAP expression, indicating a positive correlation between a reduced SAP expression and an impaired NK cell-mediated citotoxicity. In the present study it was observed that unlike patients with standard-risk, NK cells from children presenting high-risk ALL, harbor an impaired cytotoxicity towards K562 at diagnosis. In addition, NK cell function was observed to be compromised in patients with a leukocyte count ≥50,000xmm3, where also it was noticed a decreased expression of SAP compared to patients with a leukocyte count <50,000xmm3. These data indicate NK cell-mediated cytotoxicity is not equally affected in ALL patients, nevertheless a positive correlation between low SAP expression and decreased NK cell-mediated cytotoxicity was observed in ALL patients with a leukocyte count ≥50,000xmm3. Finally, an abnormal NK cell-mediated cytotoxicity may represent a prognostic factor for high-risk acute lymphoblastic leukemia.

Klíčová slova:

Acute lymphoblastic leukemia – Cancer detection and diagnosis – Cell degranulation – Cytotoxicity – Leukemias – NK cells – Pediatrics – White blood cells


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