{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:11:34Z","timestamp":1760134294645,"version":"build-2065373602"},"reference-count":65,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,26]],"date-time":"2023-11-26T00:00:00Z","timestamp":1700956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Minister of Science and Higher Education","award":["002\/RID\/2018\/19"],"award-info":[{"award-number":["002\/RID\/2018\/19"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple myeloma (MM) is a plasma cell malignancy that accounts for 1% of all cancers and is the second-most-common hematological neoplasm. Bortezomib (BTZ) is a proteasome inhibitor widely implemented in the treatment of MM alone or in combination with other agents. The development of resistance to chemotherapy is one of the greatest challenges of modern oncology. Therefore, it is crucial to discover and implement new adjuvant therapies that can bypass therapeutic resistance. In this paper, we investigated the in vitro effect of methylation inhibitor 5-Aza-2\u2032-deoxycytidine on the proliferative potential of MM cells and the development of resistance to BTZ. We demonstrate that alterations in the DNA methylation profile are associated with BTZ resistance. Moreover, the addition of methylation inhibitor 5-Aza-2\u2032-deoxycytidine to BTZ-resistant MM cells led to a reduction in the proliferation of the BTZ-resistant phenotype, resulting in the restoration of sensitivity to BTZ. However, further in vitro and ex vivo studies are required before adjuvant therapy can be incorporated into existing treatment regimens.<\/jats:p>","DOI":"10.3390\/ijms242316780","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T03:32:03Z","timestamp":1701055923000},"page":"16780","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["5-Aza-2\u2032-Deoxycytidine Alters the Methylation Profile of Bortezomib-Resistant U266 Multiple Myeloma Cells and Affects Their Proliferative Potential"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4008-7473","authenticated-orcid":false,"given":"Karolina","family":"\u0141uczkowska","sequence":"first","affiliation":[{"name":"Department of General Pathology, Pomeranian Medical University, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8695-8863","authenticated-orcid":false,"given":"Piotr","family":"Kulig","sequence":"additional","affiliation":[{"name":"Department of General Pathology, Pomeranian Medical University, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaudia","family":"Rusi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of General Pathology, Pomeranian Medical University, 70-111 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9933-5844","authenticated-orcid":false,"given":"Bart\u0142omiej","family":"Baumert","sequence":"additional","affiliation":[{"name":"Department of Hematology and Transplantology, Pomeranian Medical University, 71-252 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bogus\u0142aw","family":"Machali\u0144ski","sequence":"additional","affiliation":[{"name":"Department of General Pathology, Pomeranian Medical University, 70-111 Szczecin, Poland"},{"name":"Department of Hematology and Transplantology, Pomeranian Medical University, 71-252 Szczecin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e670","DOI":"10.1016\/S2352-3026(22)00165-X","article-title":"The epidemiological landscape of multiple myeloma: A global cancer registry estimate of disease burden, risk factors, and temporal trends","volume":"9","author":"Huang","year":"2022","journal-title":"Lancet Haematol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1080\/10428194.2017.1365859","article-title":"Managing multiple myeloma in elderly patients","volume":"59","author":"Diamond","year":"2018","journal-title":"Leuk. 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