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However, its clinical implications in multiple myeloma (MM) remain largely unexplored. We identified disulfidptosis\u2010related genes via co\u2010expression analysis and developed a risk signature through univariate Cox, least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analyses. The model was internally and externally validated for overall survival prediction. Downstream analyses included functional enrichment, tumour mutation burden (TMB), tumour microenvironment (TME) characterization and immune\u2010metabolic profiling. Preliminary in\u00a0vitro validation was conducted with\n                    <jats:italic>PLEC<\/jats:italic>\n                    \u2010knockout KMS\u201011 cells under glucose deprivation. A nine\u2010gene signature was established and validated, showing robust prognostic performance across cohorts. High\u2010risk patients displayed proliferative profiles, higher TMB, an immunosuppressive TME with neutrophils, eosinophils and exhausted T cells and activation of glycolysis and cystine\/glutathione metabolism. This signature defines an aggressive MM subtype likely unresponsive to immune checkpoint therapy. Functional assays confirmed that PLEC mediates actin disulphide cross\u2010linking during metabolic stress. We present a novel disulfidptosis\u2010related gene signature with independent prognostic value in MM, offering insights into the molecular and immune landscape of MM and serving as a useful tool for risk stratification and therapeutic suggestion.\n                  <\/jats:p>","DOI":"10.1111\/bjh.70189","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T06:10:15Z","timestamp":1759817415000},"page":"2391-2403","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A disulfidptosis\u2010related gene signature predicts prognosis and immune\u2010metabolic landscape in multiple myeloma"],"prefix":"10.1111","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9101-4245","authenticated-orcid":false,"given":"Li","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Hematology, Institute of Hematology, West China Hospital Sichuan University  Chengdu Sichuan 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