Pyruvate metabolism has prognostic potential for patients with MM. (A) Expression profiling of genes related to pyruvate metabolism at different stages of MM: MGUS (n = 22), SMM (n = 24), MM (n = 73), and relapsed MM (n = 28). Significance was determined using two-way ANOVA followed by a Dunnett test. ∗P ≤ .05; ∗∗P ≤ .005; ∗∗∗P < .0001. (B) Expression profiling of genes related to pyruvate metabolism at different stages of MM in the GSE2113 data set: MGUS (n = 6), MM (n = 20), and PCL (n = 5). Significance was determined using two-way ANOVA followed by a Dunnett test. ∗P ≤ .05; ∗∗P ≤ .005; ∗∗∗P < .0001. (C) The x-axis represents the survival time (days), and the y-axis represents survival probability (left) and progression-free survival (right). The survival analysis of the overall survival and progression-free survival in pyruvate metabolism^high and pyruvate metabolism^low groups of 772 patients with MM in the MMRF database. Significance was determined using Gehan-Breslow-Wilcoxon test. (D) Samples from patients with MM were treated with BTZ (2.5-5 nM), UK-5099 (5 μM), or the combination for 24 hours (n = 4). CD38-PE and CD45-APC-Cy7 were used to gate on MM cells. An assessment of cell viability was performed using annexin-V/DAPI staining. Significance was determined by two-way ANOVA followed by a Dunnett test. ∗P ≤ .05. (E) Schematic representing our recent findings on the contribution of the MPC complex in the response to proteasome inhibitors and function in MM cells. OXPHOS, oxidative phosphorylation; PCL, plasma cell leukemia; SMM, smoldering MM.