KLHL6 promotes chemosensitivity of DLBCL cells. (A) Schematic representation of the CRISPR screen using the CRL sgRNA library in U2932-Cas9 cells. (B) Volcano plot representing the CRISPR score and P value. The red circles represent the genes whose sgRNAs were significantly enriched in doxorubicin-treated cells (two-tailed Student t test; P ≤ .01). (C) Genes selected in panel B were evaluated for the percentages of genetic alterations in DLBCL (Duke Cancer Institute, n = 1001; Dana-Farber Cancer Institute, n = 135; Broad Institute, n = 58; The Cancer Genome Atlas PanCancer Atlas, n = 48; The Cancer Genome Atlas Firehose Legacy, n = 48; BC Cancer Canada’s Michael Smith Genome Sciences Centre, n = 53). (D) 1 × 10⁷ OCI-LY10 KLHL6^+/+ and KLHL6^–/– cells were xenografted in the flanks of NSG mice. After the average tumor volumes reached 100 mm³, mice were treated with cyclophosphamide (30 mg/kg), doxorubicin (2.48 mg/kg), and vincristine (0.38 mg/kg) IV on day 1, and prednisone (0.2 mg/kg) was given via oral gavage daily for 5 days. The experimental end point was reached when the tumor volume reached 1000 mm³. Each line represents 1 tumor in 1 mouse (n = 5 per group, two-way analysis of variance [ANOVA]). (E) Kaplan-Meier survival curves of OCI-LY10 KLHL6^+/+ and KLHL6^–/– xenografts as shown in panel D (n = 5 per group; the Mantel-Cox test). DMSO, dimethyl sulfoxide.