Single cell RNA sequencing of relapsed/refractory multiple myeloma

Most multiple myeloma patients develop refractory disease over time but the high tumor heterogeneity and complex interactions with the microenvironment make decisions on treatment challenging. Here, we have analyzed bone marrow aspirates of 20 relapsed/refractory multiple myeloma (RRMM) patients by single cell RNA-sequencing. We identify a transcriptional signature of the high-risk chromosome 1q gain and associated subclone dynamics over treatment. In the immune cell compartment, we observe an accumulation of exhausted gamma/delta T-cells and myeloid cells with immunosuppressive features. Via a co-expression analysis of receptor-ligand pairs we find that the underlying mechanisms include an upregulation of inflammatory cytokines and ligands of inhibitory receptors expressed on T and NK-cells. Finally, we identify microenvironmental changes that are specific for patients with 1q gain. Thus, our study resolves transcriptonal features of subclones in RRMM and mechanisms of microenvironmental reprogramming that can guide clinical decision making. Four WGS samples from hipo-K08K and hipo-067 were used as control.EGA study EGAS00001004805