Recognition of adult and pediatric acute lymphoblastic leukemia blasts by natural killer cells
Giovanni F. Torelli,
Nadia Peragine,
Sara Raponi,
Daria Pagliara,
Maria S. De Propris,
Antonella Vitale,
Alice Bertaina,
Walter Barberi,
Lorenzo Moretta,
Giuseppe Basso,
Angela Santoni,
Anna Guarini,
Franco Locatelli,
Robin Foà
Affiliations
Giovanni F. Torelli
Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome
Nadia Peragine
Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome
Sara Raponi
Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome
Daria Pagliara
Department of Pediatric Hematology/Oncology, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Pediatrico Bambino Gesù, Rome
Maria S. De Propris
Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome
Antonella Vitale
Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome
Alice Bertaina
Department of Pediatric Hematology/Oncology, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Pediatrico Bambino Gesù, Rome
Walter Barberi
Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome
Lorenzo Moretta
Giannina Gaslini Institute, Genova-Quarto
Giuseppe Basso
Women and Child Health Department, University of Padova
Angela Santoni
Department of Molecular Medicine, Sapienza University, Rome
Anna Guarini
Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome
Franco Locatelli
Department of Pediatric Hematology/Oncology, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Pediatrico Bambino Gesù, Rome;University of Pavia, Italy
Robin Foà
Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome
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.
