Feeding the Habit: The metabolic relationship between bone marrow mesenchymal stems cells and multiple myeloma

Multiple myeloma (MM) is an incurable malignant disease of plasma cells with the poorest 5-year survival of any haematological malignancy. Bone marrow (BM) residency of malignant plasma cells is an absolute requirement for their survival and proliferation, suggesting that the microenvironment within this niche is a critical driver of disease. We previously showed that the metabolism of the BM is significantly altered in patients with MM, and that the BM mesenchymal stem cell (BMMSC), the major supportive cell type for malignant plasma cells, was significantly and irreversibly transformed. We hypothesise that these two cell types form a co-operative metabolic network within the BM that is critical for the survival and proliferation of malignant plasma cells. If true, then targeting this metabolic communication will directly impact on disease progression and response to therapy, improving patient outcomes. We created a testable model of the metabolic network formed by malignant plasma cells and BMMSCs. Our model will identify enzymes or transporters that represent hubs, the inhibition of which would result in a breakdown of the community and sensitisation to standard therapeutic approaches to treating this incurable cancer.