title: Characteristic repartition of monocyte subsets as a diagnostic signature of chronic myelomonocytic leukemia.
abstract: Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/ myeloproliferative neoplasm whose diagnosis is currently based on the elevation of peripheral blood monocytes to >1 × 10(9)/L, measured for ≥3 months. Diagnosis can be ambiguous; for example, with prefibrotic myelofibrosis or reactive monocytosis. We set up a multiparameter flow cytometry assay to distinguish CD14(+)/CD16(-) classical from CD14(+)/CD16(+) intermediate and CD14(low)/CD16(+) nonclassical monocyte subsets in peripheral blood mononucleated cells and in total blood samples. Compared with healthy donors and patients with reactive monocytosis or another hematologic malignancy, CMML patients demonstrate a characteristic increase in the fraction of CD14(+)/CD16(-) cells (cutoff value, 94.0%). The associated specificity and sensitivity values were 95.1% and 90.6% in the learning cohort (175 samples) and 94.1% and 91.9% in the validation cohort (307 samples), respectively. The accumulation of classical monocytes, which demonstrate a distinct gene expression pattern, is independent of the mutational background. Importantly, this increase disappears in patients who respond to hypomethylating agents. We conclude that an increase in the fraction of classical monocytes to >94.0% of total monocytes is a highly sensitive and specific diagnostic marker that rapidly and accurately distinguishes CMML from confounding diagnoses.
authors: INSERM U1009, Gustave Roussy, Villejuif, France; Faculty of Medicine, University Paris-Sud, Le Kremlin-Bicêtre, France;
authors: Dorothée
authors: D
authors: Selimoglu-Buet
authors: Assistance Publique-Hôpitaux de Paris, Département d'Hématologie et d'Immunologie Biologiques, Hôpital Henri Mondor, Créteil, France; Faculté de Médecine, Université Paris-Est Créteil, Créteil, France;
authors: Orianne
authors: O
authors: Wagner-Ballon
authors: Biological Hematology, Gustave Roussy, Villejuif, France;
authors: Véronique
authors: V
authors: Saada
authors: Département of Immuno-Hématologie, Institut Cochin, Paris, France; Faculty of Medicine, Université Paris Descartes, Paris, France;
authors: Valérie
authors: V
authors: Bardet
authors: INSERM U1009, Gustave Roussy, Villejuif, France; Assistance Publique-Hôpitaux de Paris, Hématologie Clinique, Hôpital Saint-Louis, Paris, France;
authors: Raphaël
authors: R
authors: Itzykson
authors: INSERM U1009, Gustave Roussy, Villejuif, France; Faculty of Medicine, University Paris-Sud, Le Kremlin-Bicêtre, France;
authors: Laura
authors: L
authors: Bencheikh
authors: INSERM U1009, Gustave Roussy, Villejuif, France;
authors: Margot
authors: M
authors: Morabito
authors: INSERM U1009, Gustave Roussy, Villejuif, France;
authors: Elisabeth
authors: E
authors: Met
authors: Département of Immuno-Hématologie, Institut Cochin, Paris, France; Faculty of Medicine, Université Paris Descartes, Paris, France;
authors: Camille
authors: C
authors: Debord
authors: Assistance Publique-Hôpitaux de Paris, Département d'Hématologie et d'Immunologie Biologiques, Hôpital Henri Mondor, Créteil, France; Faculté de Médecine, Université Paris-Est Créteil, Créteil, France;
authors: Emmanuel
authors: E
authors: Benayoun
authors: Assistance Publique-Hôpitaux de Paris, Hématologie Clinique, Hôpital Saint-Louis, Paris, France;
authors: Anne-Marie
authors: AM
authors: Nloga
authors: Assistance Publique-Hôpitaux de Paris, Hématologie Clinique, Hôpital Saint-Louis, Paris, France;
authors: Pierre
authors: P
authors: Fenaux
authors: Assistance Publique-Hôpitaux de Paris, Hôpital Avicenne, Bobigny, France;
authors: Thorsten
authors: T
authors: Braun
authors: Clinical Hematology, Gustave Roussy, Villejuif, France;
authors: Christophe
authors: C
authors: Willekens
authors: University of Lille Nord de France, Lille, France; INSERM U837, Team 3, Cancer Research Institute of Lille, Lille, France; Clinical Hematology Unit, Centre Hospitalier Régional Universitaire de Lille, Lille, France; and.
authors: Bruno
authors: B
authors: Quesnel
authors: Assistance Publique-Hôpitaux de Paris, Hématologie Clinique, Hôpital Saint-Louis, Paris, France;
authors: Lionel
authors: L
authors: Adès
authors: Département of Immuno-Hématologie, Institut Cochin, Paris, France; Faculty of Medicine, Université Paris Descartes, Paris, France;
authors: Michaela
authors: M
authors: Fontenay
authors: INSERM US23, Unité mixte de service 2635, Analyse moléculaire, Modélisation et Imagerie de la maladie Cancereuse, and.
authors: Philippe
authors: P
authors: Rameau
authors: INSERM U1009, Gustave Roussy, Villejuif, France; INSERM US23, Unité mixte de service 2635, Analyse moléculaire, Modélisation et Imagerie de la maladie Cancereuse, and.
authors: Nathalie
authors: N
authors: Droin
authors: Biostatistics and Epidemiology Service, Gustave Roussy, Villejuif, France.
authors: Serge
authors: S
authors: Koscielny
authors: INSERM U1009, Gustave Roussy, Villejuif, France; Faculty of Medicine, University Paris-Sud, Le Kremlin-Bicêtre, France;
authors: Eric
authors: E
authors: Solary
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D017452:Receptors, IgG / Q000097:blood*; D012680:Sensitivity and Specificity
chemical_list: D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG