Minimal alterations of the myeloma cell surface proteome after CD38 loss. (A) Schematic of “antigen escape profiling” approach to reveal new cell surface therapeutic vulnerabilities in the context of CD38 downregulation. (B) Cell surface capture proteomics comparing CD38 knockdown vs nontargeting sgRNA control, with aggregated data across 3 cell lines (CRISPRi-expressing RPMI-8226, AMO1, and KMS12-PE; n = 3 replicates per cell line per sgRNA) reveals minimal changes in the cell surface proteome beyond CD38 knockdown at significance cutoff of P value <.05 and log₂ fold-change >|1.5|. (C) Integrated analysis of cell surface proteomics and mRNA-seq (n = 2 per cell line per guide) across 3 cell lines reveals the only consistent change at both protein and transcript level after CD38 knockdown is THY1/CD90 upregulation. Log₂ fold-change cutoff = |1.5|.