Concordant Shared Transcriptomic Signatures and Candidate Regulatory Features in Chronic Lymphocytic Leukemia and...

Background: Chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are B-cell malignancies with distinct cellular origins and microenvironmental dependencies. We aimed to identify concordant transcriptomic signatures and candidate transcriptional regulatory features between CLL CD19-positive B cells and MM-associated bone marrow-derived mesenchymal stromal cells (MSCs). Methods: Public Gene Expression Omnibus bulk RNA sequencing datasets were analyzed separately within each context using DESeq2. Differentially expressed genes (DEGs) were defined using adjusted p-value < 0.05 and absolute log₂ fold change > 1. Cross-disease analyses assessed overlap, directionality, log₂ fold-change concordance, expressed-gene background-adjusted enrichment, coexpression structure, and transcription factor annotation. Results: We found a focused concordant gene-level signature shared across contexts. We identified 5965 DEGs in CLL and 1021 DEGs in MM; 323 were shared, and 262 were concordantly regulated, including 52 upregulated and 210 downregulated genes in both contexts. These genes showed strong log₂ fold change concordance between CLL and MM. No Gene Ontology or Kyoto Encyclopedia of Genes and Genomes terms remained significant after expressed-gene background correction, supporting stronger gene-level than pathway-level evidence. Exploratory coexpression analysis identified PSMA3-AS1, SNORD58A, 100124516, MSS51, and 652966 as the top degree-ranked hubs and seven shared differentially expressed transcription factor candidates: MAFB, MYB, CCDC17, MYSM1, ZMAT1, ZNF491, and ZNF789. Expression-matched permutation analysis did not support global transcription factor enrichment. Conclusion: These findings support a cross-contextual concordant transcriptomic signature shared by CLL CD19-positive B cells and MM-associated MSCs, warranting validation in harmonized cohorts and experiments.