{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:17:49Z","timestamp":1785403069627,"version":"3.56.0"},"reference-count":56,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2014Next Generation EU\u2014PNRR M6C2\u2014Investment 2.1 Enhancement and strengthening of biomedical research in the NHS","award":["PNRR-MAD-2022-12376660"],"award-info":[{"award-number":["PNRR-MAD-2022-12376660"]}]},{"award":["PNRR-MAD-2022-12376660"],"award-info":[{"award-number":["PNRR-MAD-2022-12376660"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Fc\u03b3RIIIA presents a single nucleotide polymorphism at position 158 (V\/F), which affects its binding affinity to the fragment crystallizable (Fc) of antibodies (Abs). In the presence of immune complexes, Fc\u03b3RIIIA can mediate the inflammatory signaling, severity of bone disease, and osteoclastogenic activity. Based on this functional relevance, we hypothesized that the Fc\u03b3RIIIA F158V polymorphism may influence the clinical presentation of multiple myeloma (MM). Methods: Fc\u03b3RIIIA F158V genotyping was performed on genomic DNA extracted from peripheral blood samples of patients affected by MM or asymptomatic conditions named MGUS and SMM. We compared the allele frequency of Fc\u03b3RIIIA-F158V polymorphism in 72 MM, 42 MGUS and 31 SMM and evaluated the association with clinical features and occurrence of high-risk chromosome abnormalities. Targeted NGS mutation analysis was performed on genomic DNA isolated from purified CD138+ bone marrow plasma cells (BMPCs) of 41 patients, to evaluate the association between somatic mutations and the Fc\u03b3RIIIA F158V genotype. Results: the Fc\u03b3RIIIA-158 V\/V homozygous genotype was associated with high-risk cytogenetics, anemia, high beta-2 microglobulin levels, and more than 10 osteolytic lesions. V\/V homozygous genotype was significantly associated with at least one mutation in RAS pathway genes (N-RAS, K-RAS or B-RAF). In the immune microenvironment, patients carrying the V\/V homozygous genotype had a higher percentage of CD14+CD16++ non-conventional inflammatory monocytes than the V\/F or FF genotype. Conclusions: Our study contributes to a better understanding of the interactions between genetic variants, tumor microenvironment, and therapeutic response in plasma cell dyscrasias, to identify molecular biomarkers for precision medicine in MM, MGUS and SMM.<\/jats:p>","DOI":"10.3390\/cancers18071084","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T15:10:24Z","timestamp":1774537824000},"page":"1084","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fc\u03b3RIIIA Genotype in Plasma Cell Dyscrasias Is Associated with Clinical Progression, Bone Disease Extension and Immune Dysfunction"],"prefix":"10.3390","volume":"18","author":[{"given":"Daniela","family":"Cambria","sequence":"first","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Cannizzaro","sequence":"additional","affiliation":[{"name":"UOSD Radiologia, AOU Policlinico Rodolico San Marco, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nunziatina Laura","family":"Parrinello","sequence":"additional","affiliation":[{"name":"UOC Ematologia, AOU Policlinico Rodolico San Marco, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Marino","sequence":"additional","affiliation":[{"name":"UOC Ematologia, AOU Policlinico Rodolico San Marco, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Dulcamare","sequence":"additional","affiliation":[{"name":"Dipartimento di Chirurgia e Specialit\u00e0 Medico Chirurgiche, Universit\u00e0 Degli Studi di Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noemi","family":"Puccio","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Research, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1954-5695","authenticated-orcid":false,"given":"Federica","family":"Torricelli","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Research, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3342-9095","authenticated-orcid":false,"given":"Marta","family":"Lionetti","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hematology-Oncology, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Calvo","sequence":"additional","affiliation":[{"name":"Dipartimento di Chirurgia e Specialit\u00e0 Medico Chirurgiche, Universit\u00e0 Degli Studi di Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammadreza","family":"Khosropoor","sequence":"additional","affiliation":[{"name":"UOC Ematologia, AOU Policlinico Rodolico San Marco, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0862-3598","authenticated-orcid":false,"given":"Concetta","family":"Conticello","sequence":"additional","affiliation":[{"name":"UOC Ematologia, AOU Policlinico Rodolico San Marco, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Di Raimondo","sequence":"additional","affiliation":[{"name":"UOC Ematologia, AOU Policlinico Rodolico San Marco, 95123 Catania, Italy"},{"name":"Dipartimento di Chirurgia e Specialit\u00e0 Medico Chirurgiche, Universit\u00e0 Degli Studi di Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9394-2002","authenticated-orcid":false,"given":"Lavinia","family":"Raimondi","sequence":"additional","affiliation":[{"name":"Scienze e Tecnologie Chirurgiche, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7843-5969","authenticated-orcid":false,"given":"Gianluca","family":"Giavaresi","sequence":"additional","affiliation":[{"name":"Scienze e Tecnologie Chirurgiche, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1522-4504","authenticated-orcid":false,"given":"Cirino","family":"Botta","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90133 Palermo, 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":"Alessandra","family":"Romano","sequence":"additional","affiliation":[{"name":"UOC Ematologia, AOU Policlinico Rodolico San Marco, 95123 Catania, Italy"},{"name":"Dipartimento di Chirurgia e Specialit\u00e0 Medico Chirurgiche, Universit\u00e0 Degli Studi di Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1200\/JCO.2013.48.7934","article-title":"International Myeloma Working Group Consensus Statement for the Management, Treatment, and Supportive Care of Patients with Myeloma Not Eligible for Standard Autologous Stem-Cell Transplantation","volume":"32","author":"Palumbo","year":"2014","journal-title":"J. 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