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Although dysregulated lipid metabolism has been implicated in MM, its morphological correlations and clinical significance remain unclear. The present study evaluated cytoplasmic vacuoles in peripheral blood smears and analyzed their associations with the prognosis and stage of MM. Additionally, lipid droplet formation and the expression of key cholesterol regulatory molecules among MM cell lines were examined via molecular and biochemical approaches. Intracytoplasmic vacuoles were more frequently observed at advanced Revised International Staging System stages of MM, although no significant difference in overall survival was observed. MM cell lines exhibited prominent lipid droplet accumulation and upregulated acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT-1) and scavenger receptor class B type I (SR-BI) expression. The pharmacological inhibition of SR-BI suppressed MM cell proliferation and induced apoptotic cell death, whereas the inhibition of ACAT-1 had only a modest effect. Ultrastructural analysis revealed marked cytoplasmic vacuolization following SR-BI inhibition. These findings indicate that altered cholesterol metabolism is closely associated with cytoplasmic vacuolization in MM cells, suggesting that SR-BI plays a critical role in MM cell survival. Therefore, targeting the cholesterol trafficking pathways may represent a potential therapeutic strategy in MM.<\/jats:p>","DOI":"10.1007\/s00795-026-00466-2","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T08:51:33Z","timestamp":1781081493000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Scavenger receptor class B type I (SR-BI) as a potential therapeutic target in multiple myeloma"],"prefix":"10.1007","author":[{"given":"Yoshihiko","family":"Kondo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3985-0259","authenticated-orcid":false,"given":"Hiromu","family":"Yano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Niino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yawara","family":"Kawano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-ichirou","family":"Yasunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Komohara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"issue":"8","key":"466_CR1","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/nrc2189","volume":"7","author":"T Hideshima","year":"2007","unstructured":"Hideshima T, Mitsiades C, Tonon G, Richardson PG, Anderson KC (2007) Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets. 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The remaining authors have no conflicts of interest to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study design was approved by the Institutional Review Board of Kumamoto University (approval no. 2224\/3151), and conducted in accordance with the guidelines for Good Clinical Practice and the Declaration of Helsinki. Informed consent for the use of tissue samples was obtained from all participants.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}