CRISPR screening identifies MPC1 as a modulator of BTZ response in MM cells. (A) Schematic of our CRISPR-based genome-wide screening pipeline developed in MM cells. (B) Representation of the CRISPR-based dropout screen performed in U266 and JJN3 cells in the presence of BTZ (IC₂₅). Genes are represented in alphabetically order with their respective MAGeCK β-score. (C) Overlapping genes from U266 and JJN3 sensitizing arms (MAGeCK β ≤ −0.2). (D) Representation of the overlapping sensitizers identified in panel C with their respective MAGeCK β-score in JJN3 cell line (x-axis) and U266 cell line (y-axis). (E) Expression analysis of the 75 overlapping sensitizers in the MMRF CoMMpass database (n = 921). The top 9 most-expressed genes are represented in this panel. (F) Competitive growth assay in the presence or absence of BTZ (3 nM) or DMSO (vehicle) in U266 cells. Data are represented as the ratio of BFP:mCherry⁺ ± standard error of the mean, normalized to day 0 (3 different sgRNAs; n = 3). Significance was determined using two-way ANOVA followed by a Sidak test. ∗P ≤ .05; ∗∗P ≤ .01; ∗∗∗P ≤ .005. ANOVA, analysis of variance; BFP, blue fluorescent protein.