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To decipher this complexity, we performed an integrated single\u2010cell and genomic analysis. Using scRNA\u2010seq data (GSE182434), we identified six distinct malignant B\u2010cell subclusters (MB1\u2010MB6) within the DLBCL ecosystem. Cell\u2013cell communication analysis revealed intricate interaction networks, particularly involving the MIF and Complement pathways. Prognostic analysis of bulk transcriptomic data (GSE32918) identified the MB5\u2010related gene signature as the most critical factor associated with poor overall survival. This MB5 subgroup was associated with enhanced proliferative processes, a higher tumor mutational burden, and specific comutations. Leveraging MB5 marker genes, we developed and validated a robust CoxBoost\u2010RSF machine\u2010learning model that effectively stratified patient risk in independent cohorts. 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