MALT1 is highly expressed in MM cells. (A) Whole-cell lysates of human myeloma cell lines, 2 CD138⁺ primary MM cells, and 2 CD138⁻ primary BM mononuclear cells (BMMCs) were subjected to WB analysis and probed with indicated antibodies, with GAPDH as a loading control. (B) IM9 and U266 cell lines were transduced with single guide RNA (sgRNA) targeting MALT1. WB analysis of MALT1 in MALT1-KO cells (labeled as KO) compared with MALT1-scramble cells (labeled as Scr). Cell viability was measured daily by CCK-8 assay. Data are shown as optical density (OD) value at 450 nm. (C) Scramble and MALT1-KO cells were cultured with RPMI-1640 medium, HS-5 conditional medium, VEGF (100 ng/mL), insulin-like growth factor (IGF; 100 ng/mL), and IL-6 (25 ng/mL). Cell viability was measured by CCK8 assay at 24, 48, or 72 hours, and OD value at 450 nm is shown. (D) NSG mice were inoculated intravenously with scramble cells (n = 6) and MALT-KO IM9 cells (n = 6). The survival of mice was analyzed by Kaplan-Meier survival curves; hazard ratio (HR), 0.3759; 95% confidence interval (CI), 0.11-1.33. (E) The mRNA level of MALT1 in BMMCs from patients with MM or normal healthy donors (NR) was measured by quantitative reverse transcription polymerase chain reaction assay (qRT-PCR). (F) The dot blot shows the mRNA expression level of MALT1 in MM and other tumors. Data were obtained from Depmap. (G) Correlation of MALT1 with overall survival was investigated in the MMRF CoMMpass trial (772 newly diagnosed patients). No significance (ns), P > .05; ∗P < .05; ∗∗P < .005; ∗∗∗P < .001; and ∗∗∗∗P < .0001.