NKp30 expression is a prognostic immune biomarker for stratification of patients with intermediate-risk acute myeloid leukemia
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Anne-Sophie Chretien1,2, Cyril Fauriat1,2, Florence Orlanducci2, Jerome Rey3, Gaelle Bouvier Borg4, Emmanuel Gautherot4, Samuel Granjeaud5, Clemence Demerle1,2, Jean-François Hamel6, Adelheid Cerwenka7, Elke Pogge von Strandmann8,15, Norbert Ifrah9, Catherine Lacombe10, Pascale Cornillet-Lefebvre11, Jacques Delaunay12, Antoine Toubert13, Christine Arnoulet1,14, Norbert Vey1,3 and Daniel Olive1,2
1Team 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
2Immunomonitoring Platform, Institut Paoli-Calmettes, Marseille, France
3Hematology Department, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068, CNRS, UMR7258, Institut Paoli-Calmettes, Aix-Marseille University, UM 105, Marseille, France
4Beckman Coulter Immunotech, Marseille, France
5Systems Biology Platform, Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm, U1068, CNRS, UMR7258, Institut Paoli-Calmettes, Aix-Marseille University, UM 105, Marseille, France
6Biostatistics and Methodology Department, CHU Angers, Angers, France
7Innate Immunity Group, German Cancer Research Center, Heidelberg, Germany
8Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany
9Hematology Department, CHU Angers, Angers, France
10GOELAMStheque, FILO French Innovative Leukemia Organization, Cochin Hospital, APHP, Paris, France
11Laboratoire d’Hématologie, Centre Hospitalier Universitaire de Reims, Reims, France
12Service d’Hématologie, Centre Catherine de Sienne, Nantes, France
13INSERM UMRS-1160, Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d’Hématologie, Immunology and Histocompatibility Department, Hôpital Saint-Louis, APHP, Paris, France
14Biopathology Department, Institut Paoli Calmettes, Marseille, France
15Clinic for Hematology, Oncology and Immunology, Experimental Tumor Research, Center for Tumor Biology and Immunology, Philipps University, Marburg, Germany
Daniel Olive, email: email@example.com
Keywords: AML, prognostic biomarkers, natural killer, NCR, NKp30
Received: January 30, 2017 Accepted: April 26, 2017 Published: May 10, 2017
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), NKp30high 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), NKp30high 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.
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