Deregulation of Stemness and Senescence Genes in Bone Marrow Mesenchymal Stem Cells of Multiple Myeloma: Implications for Therapeutic Approaches

Purpose: Multiple myeloma (MM) is a hematologic malignancy with a poor prognosis. MM-derived MSCs (MM-MSCs) contribute to disease progression by creating a supportive stromal microenvironment for malignant cells. Therefore, elucidating transcriptomic alterations in MSCs may facilitate the development of novel therapeutic strategies for treatment resistant MM patients. Methods: Total RNA was extracted from cultured MSCs isolated from bone marrow aspirates of MM patients and normal donors (ND-MSCs). Gene expression of stemness markers ( NANOG , OCT4 ) and senescence-related genes ( P16 , P21 , IL-6 , IL-8 ) were analyzed using Reverse Transcription-Quantitative Polymerase Chain Reaction (RT-qPCR), while senescence status was assessed using SA-β-gal staining. Results: Compared to ND-MSCs, MM-MSCs demonstrated a higher percentage of SA-β-gal-positive cells. Gene expression analysis revealed upregulation of P21 and IL-6 in MM-MSCs, whereas NANOG and OCT4 were significantly downregulated. Notably, this downregulation was corroborated by analyzing a publicly available RNA-seq dataset, reinforcing our findings Conclusions: While confirming previous reports on increased senescence, our study provides novel evidence for the significant downregulation of stemness-related genes ( NANOG , OCT4 ) in MSCs from newly diagnosed, untreated MM patients. This concurrent dysregulation of stemness and increased senescent phenotype may be a key contributor to the pathogenicity of the tumor microenvironment, highlighting a potential axis for therapeutic intervention.