Research Papers:

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

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 Lecrevisse, Margarida Lima, Anton W. Langerak, Sebastian Böttcher, Jacques J.M. van Dongen, Alberto Orfao and Julia Almeida

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Oncotarget. 2015; 6:42938-42951. https://doi.org/10.18632/oncotarget.5480

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Paloma Bárcena1, María Jara-Acevedo1, María Dolores Tabernero2, Antonio López1, María Luz Sánchez1, Andrés C. García-Montero1, Noemí Muñoz-García1, María Belén Vidriales3, Artur Paiva4, Quentin Lecrevisse1, Margarida Lima5, Anton W. Langerak6, Sebastian Böttcher7, Jacques J.M. van Dongen6, Alberto Orfao1,*, Julia Almeida1,*

1Cancer Research Centre (IBMCC, CSIC-USAL), Institute of Biomedical Research of Salamanca (IBSAL), (NUCLEUS) and Department of Medicine, University of Salamanca, Salamanca, Spain

2Research Unity and IECSCYL, University Hospital of Salamanca and IBSAL, Salamanca, Spain

3Department of Hematology and Institute of Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, Salamanca, Spain

4Unidade 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.

5Department of Hematology, Laboratory of Cytometry, Hospital de Santo António, Centro Hospitalar do Porto, and Unit for Multidisciplinary Research in Biomedicine (UMIB), Porto, Portugal

6Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands

7Medical 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: [email protected]

Keywords: natural killer cells, NK cells, immunophenotype, clonality, CLPD-NK

Received: May 13, 2015     Accepted: October 27, 2015     Published: November 06, 2015


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) CD56low NK cells from 60 patients, including 23 subjects with predefined clonal (n = 9) and polyclonal (n = 14) CD56low 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 CD94hi/HLADR+ phenotypic profile proved to be a useful surrogate marker for NK-cell clonality.

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