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.
Highlights
Chronic lymphoproliferative disorders (CLPD) of natural killer (NK) cells (CLPD-NK) are a relatively rare and heterogeneous group of diseases characterized by a persistent (> 6 months) increase of matureappearing NK cells (> 2 × 109/L) in peripheral blood (PB), in the absence of a clearly identifiable cause [1, 2, 3]
In the present study we investigated the immunophenotypic profile of expanded NK cells from 23 females with predefined monoclonal and polyclonal CLPD of CD56low NK cells vs. that of normal PB NK cells, using a large panel of 26 markers analyzed by multiparameter flow cytometry; we aimed at identifying aberrant immunophenotypes that could be used as surrogate markers for NK cell clonality
Analysis of somatic mutations of the signal transducer and activator of transcription 3 and 5b genes (STAT3 and STAT5b) were consistent with the HUMARA assay, as the hotspot D661Y (c.1981G > T) mutation at the SH2 domain of STAT3 was detected in 1/4 cases carrying clonal NK cells, while no mutations were found in any of the polyclonal cases screened for STAT3 and STAT5b genes (n = 5)
Summary
Chronic lymphoproliferative disorders (CLPD) of natural killer (NK) cells (CLPD-NK) are a relatively rare and heterogeneous group of diseases characterized by a persistent (> 6 months) increase of matureappearing NK cells (> 2 × 109/L) in peripheral blood (PB), in the absence of a clearly identifiable cause [1, 2, 3]. Our results showed that despite multiple immunophenotypic differences existed between normal and expanded CD56low NK cells, the distinction between monoclonal and polyclonal NK cells mostly relied on a strong and more homogeneous pattern of expression of HLADR and CD94, typically restricted to clonal CLPD-NK
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
