Transcriptomic Profiling of Circulating Tumor Cells in Multiple Myeloma: A New Model to Understand Disease Dissemination III

The number of peripheral blood (PB) circulating tumor cells (CTCs) predicts risk of transformation in smoldering multiple myeloma (MM) and survival in active MM. Growing evidence suggests that as the tumor progresses and the microenvironment becomes hypoxic, clonal plasma cells (PCs) constantly invade new regions of the bone marrow (BM) through induced systemic recirculation. Of note, the frequency of CTCs is typically low and thus, it could be hypothesized that the dissemination of MM is made by few tumor cells with unique features that induce them to egress the BM and spread the disease through PB. This hypothesis has not been demonstrated because the molecular profile of CTCs in MM has not been investigated. Overall design: We used index sorting single-cell RNA sequencing (Precise Assay, Becton Dickinson) to identify genes and cell clusters related to disease dissemination by comparing the molecular profile of CTCs with patient-matched BM clonal PCs.