SNS-032 inhibited RNA synthesis in the CLL cells. CLL cells were incubated with 0.1, 0.3, and 1 μM SNS-032 for 6 and 24 hours, the phosphorylation of RNA Pol II and Cdk7, Cdk9 expression levels were analyzed by immunoblotting, using antibodies toward the phosphorylated Ser2 or Ser5 sites of the CTD, as well as total RNA Pol II, total Cdk7, and Cdk9. (A) A representative immunoblot from patient 4. (B) Inhibition of phosphorylation of RNA Pol II at Ser2 (■) and Ser5 (●) sites and protein levels of Cdk7 (▲) and Cdk9 (▼) after 6-hour (left) and 24-hour (right) incubation with SNS-032 from the 6 patient samples in Figure 1A. Levels of phosphorylation were quantified from the blots, normalized to total Pol II, and then expressed as a percentage of time-matched controls (mean ± SD). Levels of Cdk7 and Cdk9 were normalized to actin and expressed as percentage of time-matched controls (mean ± SD). (C) Inhibition of [³H]uridine incorporation by SNS-032 in CLL cells. The inhibition of [³H]uridine incorporation was measured in the same set of CLL samples at 6 hours (■) and 24 hours (●) in SNS-032. Data are percentage of time-matched controls (mean ± SD; n = 6 samples, each performed in triplicate). The average dpm value for untreated samples was 109 740 plus or minus 59 359 (mean ± SD).