The type 4–specific cAMP phosphodiesterase inhibitor rolipram induces apoptosis in CLL cells. (A) Time course: Rolipram (10 μmol/L) and forskolin (40 μmol/L) were added to cultures of 1 million CLL cells for the indicated time period before determination of apoptosis by Hoechst 33342 flow cytometry. (B) Dose titration: CLL cells were cultured for 72 hours in 1 mL of media with the indicated concentration of rolipram with (▪) or without (▧) the addition of 40 μmol/L forskolin. The SEMs of triplicate cultures are indicated. All of the rolipram or rolipram/forskolin-treated cultures had a significantly greater percentage of apoptotic cells than the media or forskolin-only–treated cultures, respectively (t-test: one-tailed significance level <.05).