{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T14:31:08Z","timestamp":1792593068674,"version":"4.5.0"},"reference-count":65,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014139","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer","doi-asserted-by":"publisher","award":["CB16\/12\/00400"],"award-info":[{"award-number":["CB16\/12\/00400"]}],"id":[{"id":"10.13039\/501100014139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014139","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer","doi-asserted-by":"publisher","award":["CB16\/12\/00369"],"award-info":[{"award-number":["CB16\/12\/00369"]}],"id":[{"id":"10.13039\/501100014139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014139","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer","doi-asserted-by":"publisher","award":["CB16\/12\/00233"],"award-info":[{"award-number":["CB16\/12\/00233"]}],"id":[{"id":"10.13039\/501100014139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100003887","name":"International Myeloma Foundation","doi-asserted-by":"publisher","award":["IMF13\/ IMF16"],"award-info":[{"award-number":["IMF13\/ IMF16"]}],"id":[{"id":"10.13039\/100003887","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["ERC-2015-AdG 695655"],"award-info":[{"award-number":["ERC-2015-AdG 695655"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background. Monocyte\/macrophages have been shown to be altered in monoclonal gammopathy of undetermined significance (MGUS), smoldering (SMM) and active multiple myeloma (MM), with an impact on the disruption of the homeostasis of the normal bone marrow (BM) microenvironment. Methods: We investigated the distribution of different subsets of monocytes (Mo) in blood and BM of newly-diagnosed untreated MGUS (n = 23), SMM (n = 14) and MM (n = 99) patients vs. healthy donors (HD; n = 107), in parallel to a large panel of cytokines and bone-associated serum biomarkers. Results: Our results showed normal production of monocyte precursors and classical Mo (cMo) in MGUS, while decreased in SMM and MM (p \u2264 0.02), in association with lower blood counts of recently-produced CD62L+ cMo in SMM (p = 0.004) and of all subsets of (CD62L+, CD62L\u2212 and Fc\u03b5RI+) cMo in MM (p \u2264 0.02). In contrast, intermediate and end-stage non-classical Mo were increased in BM of MGUS (p \u2264 0.03), SMM (p \u2264 0.03) and MM (p \u2264 0.002), while normal (MGUS and SMM) or decreased (MM; p = 0.01) in blood. In parallel, increased serum levels of interleukin (IL)1\u03b2 were observed in MGUS (p = 0.007) and SMM (p = 0.01), higher concentrations of serum IL8 were found in SMM (p = 0.01) and MM (p = 0.002), and higher serum IL6 (p = 0.002), RANKL (p = 0.01) and bone alkaline phosphatase (BALP) levels (p = 0.01) with decreased counts of Fc\u03b5RI+ cMo, were restricted to MM presenting with osteolytic lesions. This translated into three distinct immune\/bone profiles: (1) normal (typical of HD and most MGUS cases); (2) senescent-like (increased IL1\u03b2 and\/or IL8, found in a minority of MGUS, most SMM and few MM cases with no bone lesions); and (3) pro-inflammatory-high serum IL6, RANKL and BALP with significantly (p = 0.01) decreased blood counts of immunomodulatory Fc\u03b5RI+ cMo-, typical of MM presenting with bone lesions. Conclusions: These results provide new insight into the pathogenesis of plasma cell neoplasms and the potential role of Fc\u03b5RI+ cMo in normal bone homeostasis.<\/jats:p>","DOI":"10.3390\/cancers13061454","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T12:55:07Z","timestamp":1616417707000},"page":"1454","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Monocyte Subsets and Serum Inflammatory and Bone-Associated Markers in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9192-430X","authenticated-orcid":false,"given":"Daniela","family":"Damasceno","sequence":"first","affiliation":[{"name":"Translational and Clinical Research Program, Cancer Research Center (IBMCC, USAL-CSIC), Cytometry Service (NUCLEUS) and Department of Medicine, University of Salamanca and Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Biomedical Research Networking Centre Consortium of Oncology (CIBERONC) (CB16\/12\/00400), Instituto Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3124-8917","authenticated-orcid":false,"given":"Julia","family":"Almeida","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Program, Cancer Research Center (IBMCC, USAL-CSIC), Cytometry Service (NUCLEUS) and Department of Medicine, University of Salamanca and Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Biomedical Research Networking Centre Consortium of Oncology (CIBERONC) (CB16\/12\/00400), Instituto Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Teodosio","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, Department of Immunology, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luzalba","family":"Sanoja-Flores","sequence":"additional","affiliation":[{"name":"Biomedical Research Networking Centre Consortium of Oncology (CIBERONC) (CB16\/12\/00400), Instituto Carlos III, 28029 Madrid, Spain"},{"name":"Institute of Biomedicine of Seville, Department of Hematology, University Hospital Virgen del Roc\u00edo of the Consejo Superior de Investigaciones Cient\u00edficas (CSIC), University of Seville, 41013 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Mayado","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Program, Cancer Research Center (IBMCC, USAL-CSIC), Cytometry Service (NUCLEUS) and Department of Medicine, University of Salamanca and Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Biomedical Research Networking Centre Consortium of Oncology (CIBERONC) (CB16\/12\/00400), Instituto Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5805-1391","authenticated-orcid":false,"given":"Alba","family":"P\u00e9rez-Pons","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Program, Cancer Research Center (IBMCC, USAL-CSIC), Cytometry Service (NUCLEUS) and Department of Medicine, University of Salamanca and Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Biomedical Research Networking Centre Consortium of Oncology (CIBERONC) (CB16\/12\/00400), Instituto Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noemi","family":"Puig","sequence":"additional","affiliation":[{"name":"Biomedical Research Networking Centre Consortium of Oncology (CIBERONC) (CB16\/12\/00400), Instituto Carlos III, 28029 Madrid, Spain"},{"name":"Service of Hematology, University Hospital of Salamanca (CAUSA) and IBSAL, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Arana","sequence":"additional","affiliation":[{"name":"Regulation of the Immune System Group, Biocruces Bizkaia Health Research Institute, Hospital Universitario Cruces, Plaza de Cruces 12, 48903 Barakaldo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1977-3815","authenticated-orcid":false,"given":"Bruno","family":"Paiva","sequence":"additional","affiliation":[{"name":"Biomedical Research Networking Centre Consortium of Oncology (CIBERONC) (CB16\/12\/00400), Instituto Carlos III, 28029 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n M\u00e9dica Aplicada (CIMA), Instituto de Investigaci\u00f3n Sanitaria de Navarra (IDISNA), Clinica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Solano","sequence":"additional","affiliation":[{"name":"Hematology Service, Hospital Nuestra Se\u00f1ora del Prado, Talavera de la Reina, 45600 Toledo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Romero","sequence":"additional","affiliation":[{"name":"Primary Health Care Center \u201cMiguel Armijo\u201d, Primary Health Care of Salamanca, Conserjer\u00eda de Sanidad de Castilla y Le\u00f3n (SACYL), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Matarraz","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Program, Cancer Research Center (IBMCC, USAL-CSIC), Cytometry Service (NUCLEUS) and Department of Medicine, University of Salamanca and Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Biomedical Research Networking Centre Consortium of Oncology (CIBERONC) (CB16\/12\/00400), Instituto Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter B. L.","family":"van den Bossche","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, Department of Immunology, 2333 ZA Leiden, The Netherlands"},{"name":"Department of Immunology, Erasmus University Medical Center, 3015 GA Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1119-4387","authenticated-orcid":false,"given":"Juan","family":"Flores-Montero","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Program, Cancer Research Center (IBMCC, USAL-CSIC), Cytometry Service (NUCLEUS) and Department of Medicine, University of Salamanca and Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Biomedical Research Networking Centre Consortium of Oncology (CIBERONC) (CB16\/12\/00400), Instituto Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Durie","sequence":"additional","affiliation":[{"name":"Centro del C\u00e1ncer Cedars-Sinai Samuel Oschin, Los Angeles, CA 90048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques J. M.","family":"van Dongen","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, Department of Immunology, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0007-7230","authenticated-orcid":false,"given":"Alberto","family":"Orfao","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Program, Cancer Research Center (IBMCC, USAL-CSIC), Cytometry Service (NUCLEUS) and Department of Medicine, University of Salamanca and Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain"},{"name":"Biomedical Research Networking Centre Consortium of Oncology (CIBERONC) (CB16\/12\/00400), Instituto Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1056\/NEJMra1011442","article-title":"Multiple Myeloma","volume":"364","author":"Palumbo","year":"2011","journal-title":"N. 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