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Moreover, the partial colonization of the bone with reactive bone marrow we documented via PET-FDG imaging suggests that neoplastic cell overgrowth contributes to bone derangement. Indeed, cytokines released by leukemic B cells impair osteoblast differentiation and enhance osteoclast formation in vitro. CD16, Fc\u03b3-RIIIa, has been previously indicated as a marker of osteoclast precursors. We demonstrate, here, that the percentage of circulating monocytes, CD16+, is significantly higher in CLL patients than in normal controls and directly correlated with the extent of bone erosion. When we assessed if healthy monocytes, treated with a CLL-conditioned medium, modulated RANK, RANKL and CD16, we observed that all these molecules were up-regulated and CD16 to a greater extent. Altogether, these findings suggest that leukemic cells facilitate osteoclast differentiation. Interestingly, the evidence that monocytes, polarized toward the M2 phenotype, were characterized by high CD16 expression and showed a striking propensity to differentiate toward osteoclasts may provide further explanations for the enhanced levels of bone erosion detected, in agreement with the high number of immunosuppressive-M2 cells present in these patients.<\/jats:p>","DOI":"10.3390\/cancers14235979","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T05:31:32Z","timestamp":1670218292000},"page":"5979","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A High Percentage of CD16+ Monocytes Correlates with the Extent of Bone Erosion in Chronic Lymphocytic Leukemia Patients: The Impact of Leukemic B Cells in Monocyte Differentiation and Osteoclast Maturation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7206-376X","authenticated-orcid":false,"given":"Paolo","family":"Giannoni","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, Biology Section, University of Genova, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Marini","sequence":"additional","affiliation":[{"name":"CNR Institute of Bioimages and Molecular Physiology, 20054 Milano, Italy"},{"name":"Nuclear Medicine Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3335-1101","authenticated-orcid":false,"given":"Giovanna","family":"Cutrona","sequence":"additional","affiliation":[{"name":"Molecular Pathology Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Todoerti","sequence":"additional","affiliation":[{"name":"Hematology Unit, Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, 20122 Milano, Italy"},{"name":"Department of Pathology, IRCCS Istituto Nazionale dei Tumori G. Venezian, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Neri","sequence":"additional","affiliation":[{"name":"Scientific Directorate, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adalberto","family":"Ibatici","sequence":"additional","affiliation":[{"name":"Hematology Unit and Bone Marrow Transplantation, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianmario","family":"Sambuceti","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"},{"name":"Department of Health Sciences, University of Genova, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Pigozzi","sequence":"additional","affiliation":[{"name":"Department of Surgical and Diagnostic Sciences, University of Genova, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Mora","sequence":"additional","affiliation":[{"name":"Pathology Anatomy Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manlio","family":"Ferrarini","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Anatomy Section, University of Genova, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6643-7083","authenticated-orcid":false,"given":"Franco","family":"Fais","sequence":"additional","affiliation":[{"name":"Molecular Pathology Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"},{"name":"Department of Experimental Medicine, Anatomy Section, University of Genova, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8481-7848","authenticated-orcid":false,"given":"Daniela","family":"de Totero","sequence":"additional","affiliation":[{"name":"Molecular Pathology Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.3324\/haematol.2013.091405","article-title":"Chronic Lymphocytic Leukemia Nurse-like cells express the hepatocyte growth factor receptor (c-MET) and indoleamine 2,3-dioxygenase and display features of immunosuppressive type 2 skewed macrophages","volume":"99","author":"Giannoni","year":"2014","journal-title":"Haematologica"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.3324\/haematol.2010.029736","article-title":"An interaction between hepatocyte growth factor and its receptor (c-MET) prolongs the survival of chronic lymphocytic leukemic cells through STAT3 phosphorylation: A potential role of mesenchymal cells in the disease","volume":"96","author":"Giannoni","year":"2011","journal-title":"Haematologica"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1111\/j.1365-2141.2009.07868.x","article-title":"Bi-directional activation between mesenchymal stem cells and CLL B-cells: Implication for CLL disease progression","volume":"147","author":"Ding","year":"2009","journal-title":"Br. 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