NKp30 expression is a prognostic immune biomarker for stratification of patients with intermediate-risk acute myeloid leukemia

// Anne-Sophie Chretien 1, 2 , Cyril Fauriat 1, 2 , Florence Orlanducci 2 , Jerome Rey 3 , Gaelle Bouvier Borg 4 , Emmanuel Gautherot 4 , Samuel Granjeaud 5 , Clemence Demerle 1, 2 , Jean-François Hamel 6 , Adelheid Cerwenka 7 , Elke Pogge von Strandmann 8, 15 , Norbert Ifrah 9 , Catherine Lacombe 10 , Pascale Cornillet-Lefebvre 11 , Jacques Delaunay 12 , Antoine Toubert 13 , Christine Arnoulet 1, 14 , Norbert Vey 1, 3 and Daniel Olive 1, 2 1 Team Immunity and Cancer, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068, CNRS, UMR7258, Institut Paoli-Calmettes, Aix-Marseille University, UM 105, Marseille, France 2 Immunomonitoring Platform, Institut Paoli-Calmettes, Marseille, France 3 Hematology Department, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068, CNRS, UMR7258, Institut Paoli-Calmettes, Aix-Marseille University, UM 105, Marseille, France 4 Beckman Coulter Immunotech, Marseille, France 5 Systems Biology Platform, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068, CNRS, UMR7258, Institut Paoli-Calmettes, Aix-Marseille University, UM 105, Marseille, France 6 Biostatistics and Methodology Department, CHU Angers, Angers, France 7 Innate Immunity Group, German Cancer Research Center, Heidelberg, Germany 8 Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany 9 Hematology Department, CHU Angers, Angers, France 10 GOELAMStheque, FILO French Innovative Leukemia Organization, Cochin Hospital, APHP, Paris, France 11 Laboratoire d’Hématologie, Centre Hospitalier Universitaire de Reims, Reims, France 12 Service d’Hématologie, Centre Catherine de Sienne, Nantes, France 13 INSERM UMRS-1160, Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie, Immunology and Histocompatibility Department, Hôpital Saint-Louis, APHP, Paris, France 14 Biopathology Department, Institut Paoli Calmettes, Marseille, France 15 Clinic for Hematology, Oncology and Immunology, Experimental Tumor Research, Center for Tumor Biology and Immunology, Philipps University, Marburg, Germany Correspondence to: Daniel Olive, email: daniel.olive@inserm.fr Keywords: AML, prognostic biomarkers, natural killer, NCR, NKp30 Received: January 30, 2017 Accepted: April 26, 2017 Published: May 10, 2017 ABSTRACT Cytogenetics and European Leukemia Net (ELN) genetic classification predict patients at increased risk of relapse in acute myeloid leukemia (AML) except in the intermediate risk group for which further prognostic determinants are required. We have previously shown that Natural Killer (NK) cell defects in AML are predictors of poor overall survival (OS). This study aimins at validating NKp30, a receptor that mediates NK activation, as a prognostic biomarker for AML patients with intermediate prognosis. NKp30 expression was prospectively assessed at diagnosis on NK cells from peripheral blood by flow cytometry ( N = 201 patients). Clinical outcome was evaluated with regard to NKp30 status. In patients with intermediate cytogenetic ( N = 162), NKp30 high phenotype at diagnosis was predictive of better OS (HR = 0.26; 95%CI = [0.14-0.50]; P < 0.0001) and relapse-free survival (RFS) (HR = 0.21; 95%CI = [0.08-0.52]; P = 0.0007). In patients with intermediate ELN ( N = 116), NKp30 high phenotype at diagnosis was predictive of better OS (HR = 0.33; 95%CI = [0.16–0.67]; P = 0.0019) and RFS (HR = 0.24; 95%CI = [0.08-0.67]; P = 0.0058). In multivariate analysis, high NKp30 expression independently predicted improved OS (HR = 0.56, P = 0.046) and RFS (HR = 0.37, P = 0.048). Consistently, cumulative incidence of relapse (CIR) was lower in patients with high NKp30 expression (HR = 0.37, P = 0.026). In conclusion, we propose NKp30 status as a simple and early prognostic biomarker that identifies intermediate-risk patients with poor prognosis who otherwise may not be identified with existing risk stratification systems.