DYNAMIC INTERPLAY BETWEEN TUMOR AND MICRO-ENVIRONMENT DURING MULTIPLE MYELOMA DISEASE PROGRESSION

Characterizing the changes between normal, pre-malignant and active disease states increases our understanding of multiple myeloma (MM) pathogenesis and helps further the identification of novel preventive/therapeutic strategies. Here, using single cell multi-modal processing of whole bone marrow (BM) samples, we generated a single cell atlas of the BM from 123 individuals, including healthy volunteers, patients with monoclonal gammopathy of unknown significance (MGUS), smoldering MM (SMM) and active MM. We observed plasma cells alterations and MGUS/SMM early immune dysregulation, which increases as the disease progresses. We show evidence of population shifts in CD8+ T-cells, macrophages and classical dendritic cells. Shifts in CD8+ T-cells and macrophages were further associated with poor overall survival outcomes. We identified ligand-receptor interactions correlated to the downstream changes observed between pre-malignant and MM cells. Our findings show that myeloma tumorigenesis is associated with pathway dysregulation driven by gradual immunophenotypic changes in the tumor and tumor micro-environment.