title: Recognition of adult and pediatric acute lymphoblastic leukemia blasts by natural killer cells.
abstract: In this study, we aimed to investigate the pathways of recognition of acute lymphoblastic leukemia blasts by natural killer cells and to verify whether differences in natural killer cell activating receptor ligand expression among groups defined by age of patients, or presence of cytogenetic/molecular aberrations correlate with the susceptibility to recognition and killing. We analyzed 103 newly diagnosed acute lymphoblastic leukemia patients: 46 adults and 57 children. Pediatric blasts showed a significantly higher expression of Nec-2 (P=0.03), ULBP-1 (P=0.01) and ULBP-3 (P=0.04) compared to adult cells. The differential expression of these ligands between adults and children was confined to B-lineage acute lymphoblastic leukemia with no known molecular alterations. Within molecularly defined subgroups of patients, a high surface expression of NKG2D and DNAM1 ligands was found on BCR-ABL(+) blasts, regardless of patient age. Accordingly, BCR-ABL(+) blasts proved to be significantly more susceptible to natural killer-dependent lysis than B-lineage blasts without molecular aberrations (P=0.03). Cytotoxic tests performed in the presence of neutralizing antibodies indicated a pathway of acute lymphoblastic leukemia cell recognition in the setting of the Nec-2/DNAM-1 interaction. These data provide a biological explanation of the different roles played by alloreactive natural killer cells in pediatric versus adult acute lymphoblastic leukemia and suggest that new natural killer-based strategies targeting specific subgroups of patients, particularly those BCR-ABL(+), are worth pursuing further.
authors.affiliation: Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome torelli@bce.uniroma1.it.
authors.forename: Giovanni F
authors.initials: GF
authors.lastname: Torelli
authors.affiliation: Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome.
authors.forename: Nadia
authors.initials: N
authors.lastname: Peragine
authors.affiliation: Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome.
authors.forename: Sara
authors.initials: S
authors.lastname: Raponi
authors.affiliation: Department of Pediatric Hematology/Oncology, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Pediatrico Bambino Gesù, Rome.
authors.forename: Daria
authors.initials: D
authors.lastname: Pagliara
authors.affiliation: Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome.
authors.forename: Maria S
authors.initials: MS
authors.lastname: De Propris
authors.affiliation: Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome.
authors.forename: Antonella
authors.initials: A
authors.lastname: Vitale
authors.affiliation: Department of Pediatric Hematology/Oncology, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Pediatrico Bambino Gesù, Rome.
authors.forename: Alice
authors.initials: A
authors.lastname: Bertaina
authors.affiliation: Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome.
authors.forename: Walter
authors.initials: W
authors.lastname: Barberi
authors.affiliation: Giannina Gaslini Institute, Genova-Quarto.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.affiliation: Women and Child Health Department, University of Padova.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.affiliation: Department of Molecular Medicine, Sapienza University, Rome.
authors.forename: Angela
authors.initials: A
authors.lastname: Santoni
authors.affiliation: Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome.
authors.forename: Anna
authors.initials: A
authors.lastname: Guarini
authors.affiliation: Department of Pediatric Hematology/Oncology, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Pediatrico Bambino Gesù, Rome University of Pavia, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome.
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D008297:Male; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D010641:Phenotype; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D055815:Young Adult; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D000098862:T Lineage-Specific Activation Antigen 1; C527085:KLRK1 protein, human; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K