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Phenotypic profile of expanded NK cells in chronic lymphoproliferative disorders: a surrogate marker for NK-cell clonality

2015; Impact Journals LLC; Volume: 6; Issue: 40 Linguagem: Inglês

10.18632/oncotarget.5480

1949-2553

Paloma Bárcena, María Jara‐Acevedo, María Dolores Tabernero, Antonio López, María Luz Sánchez, Andrés C. García‐Montero, Noemí Muñoz‐García, María‐Belén Vidriales, Artur Paiva, Quentin Lécrevisse, Margarida Lima, Anton W. Langerak, Sebastian Böttcher, Jacques J. M. van Dongen, Alberto Órfão, Júlia Almeida,

Chronic Lymphocytic Leukemia Research

// Paloma Bárcena 1 , María Jara-Acevedo 1 , María Dolores Tabernero 2 , Antonio López 1 , María Luz Sánchez 1 , Andrés C. García-Montero 1 , Noemí Muñoz-García 1 , María Belén Vidriales 3 , Artur Paiva 4 , Quentin Lecrevisse 1 , Margarida Lima 5 , Anton W. Langerak 6 , Sebastian Böttcher 7 , Jacques J.M. van Dongen 6 , Alberto Orfao 1, * , Julia Almeida 1, * 1 Cancer Research Centre (IBMCC, CSIC-USAL), Institute of Biomedical Research of Salamanca (IBSAL), (NUCLEUS) and Department of Medicine, University of Salamanca, Salamanca, Spain 2 Research Unity and IECSCYL, University Hospital of Salamanca and IBSAL, Salamanca, Spain 3 Department of Hematology and Institute of Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, Salamanca, Spain 4 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. 5 Department of Hematology, Laboratory of Cytometry, Hospital de Santo António, Centro Hospitalar do Porto, and Unit for Multidisciplinary Research in Biomedicine (UMIB), Porto, Portugal 6 Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands 7 Medical Clinic II, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany * These authors have contributed equally to this work Correspondence to: Alberto Orfao, e-mail: orfao@usal.es Keywords: natural killer cells, NK cells, immunophenotype, clonality, CLPD-NK Received: May 13, 2015 Accepted: October 27, 2015 Published: November 06, 2015 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.