Bortezomib-Activated Macrophages Contribute To Multiple Myeloma Progression Via Cancer Stem Cell Enrichment

Introduction: Multiple myeloma (MM) is a progressive malignancy of plasma cells. Bortezomib, a novel proteosome inhibitor, was approved for MM treatment, demonstrating revolutionary clinical results, including a significant improvement in patient outcome. However, mechanisms involved in bortezomib resistance in case of treatment failure require investigation. We previously showed that similar to chemotherapeutic agents, bortezomib induced host effects which could contribute to MM aggressive course and relapse. Mice primed with bortezomib and subsequently implanted with MM cells exhibited increased mortality rate compared to mice injected with the vehicle control. We found that bortezomib promoted the activation of pro-inflammatory macrophages, that in turn, affected MM cell aggressiveness. The current study has explored the mechanisms through which bortezomib-activated macrophages could contribute to MM aggressiveness, with the focus on MM cancer stem cells (CSC), known to be the subset of MM cells with therapy resistance properties.