{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:45:48Z","timestamp":1790700348678,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,31]],"date-time":"2023-12-31T00:00:00Z","timestamp":1703980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The Lymphocyte-Activation Protein 3 (LAG-3) inhibitory receptor is expressed on regulatory plasma cells (PCs). Micro-environmental cells that express LAG-3 were found to be increased during the progression of smoldering multiple myeloma (SMM). To assess the possible role of LAG-3 expression on regulatory PCs in patients with plasma cell dyscrasia. Purified Cluster of Differentiation 138 (CD138+) PCs from patients with premalignant conditions, active multiple myeloma (MM), and controls were analyzed for the expression of LAG-3 by flow cytometry. Autologous CD8+T cells were incubated with sorted LAG-3pos or LAG-3neg PCs for 24 h. The expression of granzyme (Grz) in CD8+T cells was assessed by flow cytometry. LAG-3 expression on PCs in active MM (newly diagnosed and relapse refractory MM) was significantly increased compared to monoclonal gammopathy of undetermined significance (MGUS)\/ SMM. Grz expression was significantly decreased in CD8+T cells incubated with CD138+LAG-3pos PCs, compared to CD138+LAG-3neg PCs in patients with plasma cell dyscrasia, n = 31, p = 0.0041. LAG-3 expression on malignant PCs can be involved in the development of MM from MGUS by decreasing the expression of Grz in CD8+T cells.<\/jats:p>","DOI":"10.3390\/ijms25010549","type":"journal-article","created":{"date-parts":[[2023,12,31]],"date-time":"2023-12-31T06:37:12Z","timestamp":1704004632000},"page":"549","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Involvement of LAG-3positive Plasma Cells in the Development of Multiple Myeloma"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1960-9591","authenticated-orcid":false,"given":"Natalia","family":"Kreiniz","sequence":"first","affiliation":[{"name":"The Division of Hematology, Bnai Zion Medical Center, Sderot Eliyahu Golomb 47, Haifa 3339419, Israel"},{"name":"The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Efron St 1, Haifa 3525433, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasren","family":"Eiza","sequence":"additional","affiliation":[{"name":"The Proteomic Unit, Bnai Zion Medical Center, Sderot Eliyahu Golomb 47, Haifa 3104802, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3435-8612","authenticated-orcid":false,"given":"Tamar","family":"Tadmor","sequence":"additional","affiliation":[{"name":"The Division of Hematology, Bnai Zion Medical Center, Sderot Eliyahu Golomb 47, Haifa 3339419, Israel"},{"name":"The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Efron St 1, Haifa 3525433, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilana","family":"Levy Yurkovski","sequence":"additional","affiliation":[{"name":"The Division of Hematology, Bnai Zion Medical Center, Sderot Eliyahu Golomb 47, Haifa 3339419, Israel"},{"name":"The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Efron St 1, Haifa 3525433, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0517-693X","authenticated-orcid":false,"given":"Sarah","family":"Matarasso Greenfeld","sequence":"additional","affiliation":[{"name":"The Division of Hematology, Bnai Zion Medical Center, Sderot Eliyahu Golomb 47, Haifa 3339419, Israel"},{"name":"The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Efron St 1, Haifa 3525433, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adi","family":"Sabag","sequence":"additional","affiliation":[{"name":"The Proteomic Unit, Bnai Zion Medical Center, Sderot Eliyahu Golomb 47, Haifa 3104802, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raeda","family":"Mubariki","sequence":"additional","affiliation":[{"name":"The Proteomic Unit, Bnai Zion Medical Center, Sderot Eliyahu Golomb 47, Haifa 3104802, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Suriu","sequence":"additional","affiliation":[{"name":"The Division of Hematology, Galilee Medical Center, Nahariya-Cabri 89, Nahariyya 221001, Israel"},{"name":"Azrieli Faculty of Medicine, Bar-Ilan University, Henrietta Szold St 8, Safed 1311502, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Votinov","sequence":"additional","affiliation":[{"name":"The Division of Hematology, Kaplan Medical Center, Derech Pasternak 1, Rehovot 7610001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Toubi","sequence":"additional","affiliation":[{"name":"The Proteomic Unit, Bnai Zion Medical Center, Sderot Eliyahu Golomb 47, Haifa 3104802, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahava","family":"Vadasz","sequence":"additional","affiliation":[{"name":"The Proteomic Unit, Bnai Zion Medical Center, Sderot Eliyahu Golomb 47, Haifa 3104802, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17046","DOI":"10.1038\/nrdp.2017.46","article-title":"Multiple myeloma","volume":"3","author":"Kumar","year":"2017","journal-title":"Nat. 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