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However, the mechanisms linking monocyte dysfunction to immune evasion remain incompletely understood. In this study, single\u2010cell RNA sequencing (scRNA\u2010seq) of peripheral blood (PB) and bone marrow (BM) monocytes was\u00a0performed from healthy donors (HDs) and MM patients to generate a comprehensive single\u2010cell transcriptional map. Although PB and BM monocytes displayed comparable cellular compositions, MM monocytes exhibited marked transcriptional alterations, most prominently within the type I interferon (IFN) signaling pathway. Trajectory analyses revealed IFN\u2010driven disruptions in monocyte differentiation and developmental trajectories in both PB and BM compartments. Functional co\u2010culture assays demonstrated that activation of the type I IFN pathway enhanced MM cell proliferation, suggesting that IFN\u2010mediated monocyte reprogramming facilitates tumor progression. In an independent validation cohort, longitudinal sampling before and after induction therapy confirmed that anti\u2010myeloma treatment alleviated the excessive IFN response of BM monocytes. Collectively, these findings uncover a mechanistic link between aberrant IFN activation and monocyte dysregulation in MM, providing new insights into immune dysfunction and highlighting the IFN pathway as a potential therapeutic target to restore anti\u2010tumor immunity.<\/jats:p>","DOI":"10.1002\/advs.202510816","type":"journal-article","created":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T16:56:30Z","timestamp":1764521790000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Type I Interferon Pathway Activation Disrupts Monocyte Maturation and Enhances Immune Evasion in Multiple Myeloma"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3885-6782","authenticated-orcid":false,"given":"Jian","family":"Cui","sequence":"first","affiliation":[{"name":"State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell 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