摘要：SummaryDespite recent therapeutic advances for multiple myeloma (MM), relapse is very common. Here, we conducted longitudinal single-cell transcriptome sequencing (scRNA-seq) of MM cells from a patient with relapsed MM, treated with multiple anti-myeloma drugs. We observed five subclusters of MM cells, which appeared and/or disappeared in response to the therapeutic pressure, and identified cluster 3 which emerged during lenalidomide treatment and disappeared after proteasome inhibitor (PI) treatment. Among the differentially expressed genes in cluster 3, we found a candidate drug-response gene; pellino E3 ubiquitin-protein ligase family member 2 (PELI2), which is responsible for PI-induced cell death inin vitroassay. Kaplan-Meier survival analysis of database revealed that higher expression ofPELI2is associated with a better prognosis. Our integrated strategy combining longitudinal scRNA-seq analysis,in vitrofunctional assay, and database analysis would facilitate the understanding of clonal dynamics of MM in response to anti-myeloma drugs and identification of drug-response genes.Graphical abstractDisplay OmittedHighlights•Longitudinal scRNA-seq reveals clonal dynamics of MM under therapeutic pressure•PELI2is identified as a candidate proteasome inhibitors (PI)-sensitive gene from the PI-sensitive cluster•Overexpression ofPELI2sensitizes PI to an MM cell line in the cytotoxic assay•In database analysis, high expression ofPELI2is associated with a better prognosisDrugs; Cancer; Omics
