DLBCL subsets exhibit different sensitivities to pracinostat. (A) The in vivo activity of pracinostat was assessed in the TMD8 DLBCL xenograft model. Pracinostat significantly delayed tumor growth after 3 days of treatment. Boxplots represent tumor volumes (mm³) for vehicle- and pracinostat-treated mice. Midlines indicate the median, upper and lower perimeters indicate the 25th and 75th percentiles, and tails indicate minimum and maximum values. (B) Individual IC₅₀ values for DLBCLs are shown. High-sensitivity (IC₅₀ ≤ 0.5 × median IC₅₀) and low-sensitivity (IC₅₀ ≥ 2 × median IC₅₀) DLBCLs are highlighted in the blue boxes. Red bars correspond to OxPhos-DLBCLs. (C) Functional annotation analysis to compare low-sensitivity (IC₅₀ ≥ 2 × median IC₅₀ for pracinostat) vs high-sensitivity (IC₅₀ ≤ 0.5 × median IC₅₀ for pracinostat) DLBCLs revealed an enrichment of fatty acid metabolism–related transcripts in low-sensitivity DLBCLs (left, red bars). High-sensitivity DLBCLs (right) were enriched for immune-related pathways (yellow bars). Cell cycle and apoptosis-related pathways (blue bars) were enriched in both low- and high-sensitivity DLBCLs. The top 10 enriched Hallmark gene sets (P < .05 and false discovery rate < .05) are shown for each sensitivity group. (D) Comparison of IC₅₀ values for BCR-DLBCLs and OxPhos-DLBCLs showed that OxPhos-DLBCLs were significantly less sensitive to pracinostat and vorinostat than were BCR-DLBCLs. Comparison of ABC-DLBCLs and GCB-DLBCLs showed that these molecular subtypes exhibited similar sensitivities to HDACis. The midlines indicate the median, upper and lower perimeters indicate the 25th and 75th percentiles, and tails indicate minimum and maximum values. Two-sided Student t test: *P < .05; **P < .01; ***P < .001.