title: Phenotypic profile of expanded NK cells in chronic lymphoproliferative disorders: a surrogate marker for NK-cell clonality.
abstract: Currently, the lack of a universal and specific marker of clonality hampers the diagnosis and classification of chronic expansions of natural killer (NK) cells. Here we investigated the utility of flow cytometric detection of aberrant/altered NK-cell phenotypes as a surrogate marker for clonality, in the diagnostic work-up of chronic lymphoproliferative disorders of NK cells (CLPD-NK). For this purpose, a large panel of markers was evaluated by multiparametric flow cytometry on peripheral blood (PB) CD56(low) NK cells from 60 patients, including 23 subjects with predefined clonal (n = 9) and polyclonal (n = 14) CD56(low) NK-cell expansions, and 37 with CLPD-NK of undetermined clonality; also, PB samples from 10 healthy adults were included. Clonality was established using the human androgen receptor (HUMARA) assay. Clonal NK cells were found to show decreased expression of CD7, CD11b and CD38, and higher CD2, CD94 and HLADR levels vs. normal NK cells, together with a restricted repertoire of expression of the CD158a, CD158b and CD161 killer-associated receptors. In turn, NK cells from both clonal and polyclonal CLPD-NK showed similar/overlapping phenotypic profiles, except for high and more homogeneous expression of CD94 and HLADR, which was restricted to clonal CLPD-NK. We conclude that the CD94(hi)/HLADR+ phenotypic profile proved to be a useful surrogate marker for NK-cell clonality.
authors.affiliation: Cancer Research Centre (IBMCC, CSIC-USAL), Institute of Biomedical Research of Salamanca (IBSAL), (NUCLEUS) and Department of Medicine, University of Salamanca, Salamanca, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Bárcena
authors.affiliation: Cancer Research Centre (IBMCC, CSIC-USAL), Institute of Biomedical Research of Salamanca (IBSAL), (NUCLEUS) and Department of Medicine, University of Salamanca, Salamanca, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Jara-Acevedo
authors.affiliation: Research Unity and IECSCYL, University Hospital of Salamanca and IBSAL, Salamanca, Spain.
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Tabernero
authors.affiliation: Cancer Research Centre (IBMCC, CSIC-USAL), Institute of Biomedical Research of Salamanca (IBSAL), (NUCLEUS) and Department of Medicine, University of Salamanca, Salamanca, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: López
authors.affiliation: Cancer Research Centre (IBMCC, CSIC-USAL), Institute of Biomedical Research of Salamanca (IBSAL), (NUCLEUS) and Department of Medicine, University of Salamanca, Salamanca, Spain.
authors.forename: María Luz
authors.initials: ML
authors.lastname: Sánchez
authors.affiliation: Cancer Research Centre (IBMCC, CSIC-USAL), Institute of Biomedical Research of Salamanca (IBSAL), (NUCLEUS) and Department of Medicine, University of Salamanca, Salamanca, Spain.
authors.forename: Andrés C
authors.initials: AC
authors.lastname: García-Montero
authors.affiliation: Cancer Research Centre (IBMCC, CSIC-USAL), Institute of Biomedical Research of Salamanca (IBSAL), (NUCLEUS) and Department of Medicine, University of Salamanca, Salamanca, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Muñoz-García
authors.affiliation: Department of Hematology and Institute of Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, Salamanca, Spain.
authors.forename: María Belén
authors.initials: MB
authors.lastname: Vidriales
authors.affiliation: Unidade de Gestão Operacional em Citometria, Serviço de Patologia Clínica, Centro Hospitalar e Universitário de Coimbra, Instituto Politécnico de Coimbra, ESTESC-Coimbra Health School, Análises Clínicas e Saúde Pública, Coimbra,Portugal.
authors.forename: Artur
authors.initials: A
authors.lastname: Paiva
authors.affiliation: Cancer Research Centre (IBMCC, CSIC-USAL), Institute of Biomedical Research of Salamanca (IBSAL), (NUCLEUS) and Department of Medicine, University of Salamanca, Salamanca, Spain.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Lecrevisse
authors.affiliation: Department of Hematology, Laboratory of Cytometry, Hospital de Santo António, Centro Hospitalar do Porto, and Unit for Multidisciplinary Research in Biomedicine (UMIB), Porto, Portugal.
authors.forename: Margarida
authors.initials: M
authors.lastname: Lima
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Anton W
authors.initials: AW
authors.lastname: Langerak
authors.affiliation: Medical Clinic II, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Böttcher
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Jacques J M
authors.initials: JJ
authors.lastname: van Dongen
authors.affiliation: Cancer Research Centre (IBMCC, CSIC-USAL), Institute of Biomedical Research of Salamanca (IBSAL), (NUCLEUS) and Department of Medicine, University of Salamanca, Salamanca, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
authors.affiliation: Cancer Research Centre (IBMCC, CSIC-USAL), Institute of Biomedical Research of Salamanca (IBSAL), (NUCLEUS) and Department of Medicine, University of Salamanca, Salamanca, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Almeida
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis*; D002908:Chronic Disease; D002999:Clone Cells / Q000473:pathology; D016000:Cluster Analysis; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000473:pathology*; D008232:Lymphoproliferative Disorders / Q000175:diagnosis*; D008875:Middle Aged; D010641:Phenotype; D011944:Receptors, Androgen / Q000032:analysis
chemical_list: C410798:AR protein, human; D015415:Biomarkers; D011944:Receptors, Androgen
keywords: CLPD-NK; NK cells; clonality; immunophenotype; natural killer cells