The role of bone marrow derived bystander cells in the development of multiple myeloma

Multiple Myeloma (MM) is a hematological cancer hallmarked by the clonal expansion of malignant plasma cells in the bone marrow (BM). Despite significant therapeutic advances, MM remains an incurable disease for the majority of patients due to an incomplete eradication of residual cancer cells and/or acquired drug resistance. It is now well-established that the BM constitutes a microenvironment required for development, maintenance, proliferation and drug resistance of MM cells. In the past decade, proteasome inhibitors as well as immunomodulatory agents significantly increased the survival of MM patients by targeting both the BM microenvironment and the MM cells. This emphasizes the need for further investigation of the MM-BM interactions to develop new targeted therapies. The aim of this PhD thesis was to study bystander cells of the BM niche in their potential to stimulate myeloma progression and drug resistance. We used the immunocompetent 5TMM mouse model that resembles the human disease closely and allows the ability to investigate the interactions between MM cells and the BM microenvironment. We focused on the role of myeloid derived suppressor cells (MDSC), cancer associated fibroblasts (CAFs) and mesenchymal stromal cells in the development of MM disease.