N-Azacytidine Inhibits Myeloma Cell Growth While Preserving Multiple Myeloma Patient Derived-Bone Marrow Mesenchymal Stromal Cells Differentiation

Background/Objectives: Multiple myeloma (MM) is an incurable, hematological malignancy caused by the abnormal proliferation of terminally differentiated plasma cells in the bone marrow. Current research indicates that N-azacytidine, as an epigenetic drug and nucleoside metabolic inhibitor, can be efficient in MM treatment. However, data on bone marrow mesenchymal stromal cells (BMSCs), as a critical cell population in the hematopoiesis and bone remodeling processes, are limited. Methods: The effect of N-azacytidine on the myeloma cell line AMO-1, bone marrow mesenchymal stromal cells from MM patients (MM-MSCs) and patients undergoing hip arthroplasty (BMSCs) as a healthy control in hypoxia (3% O2) were examined. Cellular functions such as viability, proliferation, phenotype, and differentiation were determined by in vitro tests and flow-cytometry. Results: N-azacytidine (100 nM to 1000 nM) significantly inhibited metabolic activity, cell cycle, CFSE dilution and CD138+/CD38+ expression levels by myeloma cells after 72 h. No viability changes were detected in MM-MSCs and BMSCs treated with N-azacytidine. As for both BMSCs and MM-MSCs differentiation potential, N-azacytidine did not affect alkaline phosphatase (ALP) activity and adipogenesis but inhibited matrix mineralization (500 nM and 1000 nM). However, when BMSCs were pretreated with N-azacytidine for 72 h, changes in ALP activity and mineralization level were not detected. Conclusions: N-azacytidine, along with the suppressive effect on myeloma cells, did not change the differentiation potential of MSCs, but rather preserved their capacity. These findings are of particular importance considering MM progression and bone tissue destruction, suggesting that N-azacytidine may represent a promising therapeutic agent for myeloma disease.