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MM-derived mesenchymal stromal cells (MM-MSCs) contribute to disease progression by creating a supportive stromal microenvironment for malignant cells. Elucidating transcriptomic alterations in MSCs may therefore facilitate the development of novel therapeutic strategies for treatment-resistant MM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Total RNA was extracted from cultured MSCs isolated from bone marrow aspirates of patients with MM and normal donors (ND-MSCs). Expression of stemness markers (\n                      <jats:italic>NANOG<\/jats:italic>\n                      ,\n                      <jats:italic>OCT4<\/jats:italic>\n                      ) and senescence-associated genes (\n                      <jats:italic>P16<\/jats:italic>\n                      ,\n                      <jats:italic>P21<\/jats:italic>\n                      ,\n                      <jats:italic>IL-6<\/jats:italic>\n                      ,\n                      <jats:italic>IL-8<\/jats:italic>\n                      ) was analyzed using reverse transcription-quantitative polymerase chain reaction. Cellular senescence was assessed by senescence-associated \u03b2-galactosidase (SA-\u03b2-gal) staining.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared with ND-MSCs, MM-MSCs demonstrated a higher percentage of SA-\u03b2-gal-positive cells. Gene expression analysis showed upregulation of\n                      <jats:italic>P21<\/jats:italic>\n                      and\n                      <jats:italic>IL-6<\/jats:italic>\n                      in MM-MSCs, whereas\n                      <jats:italic>NANOG<\/jats:italic>\n                      and\n                      <jats:italic>OCT4<\/jats:italic>\n                      were significantly downregulated. Notably, this downregulation was consistent with analysis of a publicly available RNA sequencing dataset, supporting the validity of our findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Consistent with previous reports of increased senescence, our findings demonstrate significant downregulation of stemness-related genes (\n                      <jats:italic>NANOG<\/jats:italic>\n                      ,\n                      <jats:italic>OCT4<\/jats:italic>\n                      ) in MSCs from newly diagnosed, untreated patients with MM. This concurrent dysregulation of stemness and increased senescent phenotype may contribute to the pathogenicity of the tumor microenvironment and represents a potential target for therapeutic intervention.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>Not applicable. This study did not involve a clinical trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s44313-026-00128-3","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T03:08:13Z","timestamp":1778123293000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deregulation of stemness and senescence genes in bone marrow mesenchymal stem cells of multiple myeloma: implications for therapeutic approaches"],"prefix":"10.1007","volume":"61","author":[{"given":"Fatemeh","family":"Soleymani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saeideh","family":"Kavousi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nastaran","family":"Khodakarim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Ahmadvand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"128_CR1","unstructured":"SEER Program, NCI. 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