GSI reduced BCMA shedding from plasma cells in patients without effect on TNFRSF17 mRNA expression. (A-B) Box plots comparing the percentage of tumor and normal plasma cells expressing TNFRSF17 (A) and the normalized TNFRSF17 expression (B). Paired Wilcoxon rank-sum P values are shown for each comparison between time points. (C) Box plots comparing the percentage of plasma cells expressing BCMA using flow cytometry. (D) Box plots comparing the percentage of tumor and normal plasma cells with accessible chromatin in the TNFRSF17 gene body or promoter regions before and after exposure to GSI. (E) Normalized TNFRSF17 gene activity (counts within gene body or promoter regions) before and after exposure to GSI. (F) Box plots comparing BCMA MFI before and after exposure to GSI. (G) Density plots of normalized TNFRSF17 expression for each tumor cell subclone inferred by clustering of copy number variants. An asterisk to the left of the density plot indicates that its TNFRSF17 expression significantly differed from normal plasma cells (eg, plasma cells without aneuploidy) using the MAST statistical framework. (H) Density plots of normalized TNFRSF17 expression according to the number of copies of TNFRSF17. Amp, amplification; Del, deletion; Neu, neutral.