Primary bone marrow stromal cells in plasma cell disorders

Multiple myeloma (MM) and its premalignant precursor MGUS (monoclonal gammopathy of undetermined significance) are clonal plasma cell diseases that develop in the bone marrow (BM) and are dependent on microenvironmental interactions. Primary bone marrow stromal cells (BMSCs) are key players in the BM microenvironment, however, their role in MGUS/MM pathophysiology is not known. We therefore investigated potential disease-specific alterations in prospectively isolated BMSCs from MM, MGUS and healthy controls. Clear disease-related BMSC surface marker and gene expression differences were recorded, and deep sequencing identified shared MGUS/MM as well as MM-specific molecular signatures. Moreover, we identified genes that were deregulated in a disease-stage manner, thus reflecting the progression from normal to MGUS and MM. Analysis of primary BMSCs revealed disease-stage related protein and gene expression patterns, which provides novel insight into the stromal transitions and their functional implications for plasma cell disease development and progression. RNA sequencing data from primary prospectively-isolated and bulk-sorted bone marrow stromal cells (BMSCs) defined as lin-CD45-CD71-CD235a-CD31-CD271+ from multiple myeloma (MM, n=10) and MGUS (n=5) patients in comparison with older healthy donor (n=7) BMSCs Submitter declares that the raw data will be submitted to EGA because of patient privacy concerns.