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The bone marrow barrier (BMB) plays a pivotal role in plasma cell homing and disease progression. Bone marrow endothelial cells (BMECs) and bone marrow stromal cells (BMSCs), through their interactions with MM cells, secrete adhesion molecules, angiogenic cytokines, anti-apoptotic factors, and growth-promoting signals that support MM cell survival and proliferation. This review examines the components of the BMB and the major pathways involved in MM pathogenesis. Targeting the interactions between MM cells and the BMB may offer novel therapeutic opportunities.<\/jats:p>","DOI":"10.3390\/ijms26157301","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T16:00:37Z","timestamp":1753718437000},"page":"7301","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Breaking Barriers: The Role of the Bone Marrow Microenvironment in Multiple Myeloma Progression"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8253-0598","authenticated-orcid":false,"given":"Aleksandra","family":"Agafonova","sequence":"first","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9920-8310","authenticated-orcid":false,"given":"Chiara","family":"Prinzi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2377-858X","authenticated-orcid":false,"given":"Angela","family":"Trovato Salinaro","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Clinical Biochemistry, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0739-8798","authenticated-orcid":false,"given":"Caterina","family":"Ledda","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Occupational Medicine, University of Catania, 95124 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1709-5874","authenticated-orcid":false,"given":"Alessia","family":"Cosentino","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7541-656X","authenticated-orcid":false,"given":"Maria Teresa","family":"Cambria","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7951-1812","authenticated-orcid":false,"given":"Carmelina Daniela","family":"Anfuso","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9291-6969","authenticated-orcid":false,"given":"Gabriella","family":"Lupo","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1097\/MOH.0000000000000621","article-title":"Structural Organization of the Bone Marrow and Its Role in Hematopoiesis","volume":"28","author":"Lucas","year":"2021","journal-title":"Curr. 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