{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T07:06:47Z","timestamp":1769152007874,"version":"3.49.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002943","name":"Departament d'Innovaci\u00f3, Universitats i Empresa, Generalitat de Catalunya","doi-asserted-by":"publisher","award":["2014\/SGR585"],"award-info":[{"award-number":["2014\/SGR585"]}],"id":[{"id":"10.13039\/501100002943","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002943","name":"Departament d'Innovaci\u00f3, Universitats i Empresa, Generalitat de Catalunya","doi-asserted-by":"publisher","award":["2017\/SGR437"],"award-info":[{"award-number":["2017\/SGR437"]}],"id":[{"id":"10.13039\/501100002943","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Lab Hematology"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Dysregulated NK cell\u2010mediated immune responses contribute to tumor evasion in chronic lymphocytic leukemia (CLL), although the NK cell compartment in CLL\u2010like monoclonal B\u2010cell lymphocytosis (MBL) is poorly understood. In healthy individuals, human cytomegalovirus (HCMV) induces the expansion of NK cells expressing high levels of CD94\/NKG2C NK cell receptor (NKR) specific for HLA\u2010E.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed the expression of NKG2A, NKG2C, ILT2, KIR, CD161, and CD57 in 24 MBL and 37 CLL. <jats:italic>NKG2C<\/jats:italic> was genotyped in these patients and in 81 additional MBL\/CLL, while <jats:italic>NKG2C<\/jats:italic> gene expression was assessed in 26 cases. In 8 CLL patients with increased lymphocytosis (\u226520\u00a0\u00d7\u00a010<jats:sup>9<\/jats:sup>\/L), tumor HLA\u2010E and HLA\u2010G expression was evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>NKR distribution did not significantly differ between MBL and CLL patients, although they exhibited reduced NKG2C<jats:sup>+<\/jats:sup> NK cells compared with a non\u2010CLL group (4.6% vs 12.2%, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.012). HCMV<jats:sup>+<\/jats:sup> patients showed increased percentages of NKG2C<jats:sup>+<\/jats:sup> NK cells compared with HCMV<jats:sup>\u2212<\/jats:sup> (7.3% vs 2.9%, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.176). Frequencies of <jats:italic>NKG2C<\/jats:italic> deletions in MBL\/CLL were similar to those of the general population. Low\/undetectable NKG2C expression was found among <jats:italic>NKG2C<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> (45%) and <jats:italic>NKG2C<\/jats:italic><jats:sup>+\/+<\/jats:sup> (12%) patients. CLL cases with increased lymphocytosis displayed especially reduced NKG2C expression (1.8% vs 8.1%, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.029) and tumor cells with high HLA\u2010E (&gt;98%) and variable HLA\u2010G expression (12.4%, range: 0.5\u201056.4). CLL patients with low NKG2C expression (&lt;7%) showed shorter time to first treatment (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.037).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Reduced percentages of CD94\/NKG2C<jats:sup>+<\/jats:sup> NK cells were observed in CLL and MBL patients independently of HCMV serostatus and <jats:italic>NKG2C<\/jats:italic> zygosity, particularly in CLL patients with increased lymphocytosis, which could potentially be related to the exposure to tumor cells.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ijlh.13494","type":"journal-article","created":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T08:50:32Z","timestamp":1613983832000},"page":"1032-1040","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Reduced expansion of CD94\/NKG2C<sup>+<\/sup> NK cells in chronic lymphocytic leukemia and CLL\u2010like monoclonal B\u2010cell lymphocytosis is not related to increased human cytomegalovirus seronegativity or <i>NKG2C<\/i> deletions"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9627-4978","authenticated-orcid":false,"given":"Anna","family":"Puiggros","sequence":"first","affiliation":[{"name":"Molecular Cytogenetics Laboratory Hematological Cytology Laboratory Pathology Department Hospital del Mar Barcelona Spain"},{"name":"Translational Research on Hematological Neoplasms Group Cancer Research Program IMIM\u2010Hospital del Mar Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gonzalo","family":"Blanco","sequence":"additional","affiliation":[{"name":"Molecular Cytogenetics Laboratory Hematological Cytology Laboratory Pathology Department Hospital del Mar Barcelona Spain"},{"name":"Translational Research on Hematological Neoplasms Group Cancer Research Program IMIM\u2010Hospital del Mar Barcelona 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