Stromal and Endothelial Transcriptional Changes during Progression from MGUS to Myeloma and after Treatment Response [RNA-Seq]

The role of the non-immune bone marrow microenvironment (BME) in the transition from monoclonal gammopathy of undetermined significance (MGUS) into clinically active multiple myeloma (MM) remains incompletely defined. To address this, we transcriptionally profiled endothelial cells (EC), mesenchymal stem cells (MSC), and MM cells at single-cell resolution from genetically engineered mouse models (BIc1 and MIc1) that recapitulate MGUS to MM progression. Our analysis of the BIc1 model revealed distinct transcriptional alterations in EC and MSC, uncovering stage-specific BME-PC interactions shaping disease progression. Interestingly, we identified an interferon (IFN)-related myeloma signature in both EC and MSC that was reversed after treatment with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd).