NPI-0052 synergizes with HDAC inhibitors in primary and cultured leukemia cells. (A) Synergistic interactions between NPI-0052 and vorinostat. Jurkat cells were treated with indicated low doses of NPI-0052 and vorinostat for 24 hours. After PI cell staining, DNA fragmentation was assessed by flow cytometry. The averages of 3 independent experiments were taken to determine synergy by calculating the combination index value (CI) by isobologram analysis with Calcusyn software. A CI less than 1.0 indicates synergism. Table defines dose combinations for each data point shown and CI values. (B) HDAC inhibitors synergize more effectively with NPI-0052 than bortezomib in one AML patient sample. Mononuclear cells isolated from peripheral blood from an AML patient were treated with an HDACi/proteasome inhibitor regimen as indicated for 24 hours. DNA fragmentation was assessed after PI staining. Shown is the percent increase in the subdiploid population. CI values, indicating synergy, for each combination are shown above each bar.