Figure 1 from CD70-Targeting CAR NK Cells Overcome BCMA Downregulation and Improve Survival in High-risk Multiple Myeloma Models

CD70 expression in patients with multiple myeloma. Comparison of CD70 mRNA levels based on (A) RNA levels from the MMRF CoMMpass dataset of different translocations, Amp1q and Del17p, in patients with NDMM and (B) the ISS (n = 561). C, Paired comparison of CD70 mRNA in NDMM and at first relapse (left). The difference between the expression levels is plotted (right, relapsed–NDMM) with a dotted line at the mean of differences (0.609, P = 0.0028, paired t test, n = 61). D, Patients were stratified into tertiles based on CD70 mRNA expression, and overall survival (OS) was plotted (n = 792). Color shading represents the 95% confidence interval. E, Bone marrow aspirates from patients with multiple myeloma (n = 46) from the MD Anderson Cancer Center with different translocations involving chromosome 14 were analyzed for CD70 mRNA using the pseudobulk approach on single cell (sc)-mRNA. The control group included samples from n = 3 healthy control donors. The fourth data point in the control group represents nontumor or polyclonal plasma cells (PC) from patients with multiple myeloma identified by the expression of B-cell receptor VDJ using scRNA-seq (see “Methods”); monoclonal plasma cells were similarly defined based on BCR VDJ sequences, and each remaining data point corresponds to an individual patient with multiple myeloma: no translocation (none; n = 20), t(11;14) (n = 16), t(14;16) (n = 2), and t(4;14) (n = 8). F, The sc-mRNA transcriptome data from all samples projected onto a Uniform Manifold Approximation and Projection for Dimension Reduction (UMAP). Individual CD70 mRNA was mapped at single-cell resolution. G, Translocations involving the immunoglobulin heavy chain locus identified by FISH are mapped onto a UMAP. Box and whisker plots show the median and IQR (25th and 75th percentiles), and the whiskers extend to ±1.5 times the IQR. The P values were determined by the Wilcoxon test [A, B, D (left panel) and E]. *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001; ns, not significant. UMI, unique molecular identifier.