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Introduction Patients with Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM) exhibit variable risk of progression to full-blown Multiple Myeloma (MM), which cannot be fully explained by differences in tumor burden or genetic alterations. Therefore, characterizing non-genetic changes in malignant plasma cells may help to identify novel mechanisms of disease progression and improve prognostication. Our current understanding of transcriptomic alterations in patients with MGUS and SMM is based on bulk RNA-sequencing or microarray studies, which are affected by sample purity and interpatient variability. Here, we present results from the largest single-cell RNA-sequencing cohort (n= 245) of tumor samples from patients with MGUS and SMM.

Methods We performed single-cell RNA-and V (D) J-sequencing on 245 samples from 36 patients with MGUS, 136 …