Directly targeting RRM2 induces PEL apoptosis through causing DNA damage. (A) BCP-1 and BCBL-1 were transfected with either negative control siRNA (n-siRNA) or RRM2-siRNA for 48 hours, then cell apoptosis was assessed using Annexin V-PI staining and flow cytometry analysis. (B-C) Protein expression was measured by immunoblots and immunofluorescence, respectively. (D-E) Cells were treated with indicated concentrations of RRM2 inhibitor, 3-AP, for 24 hours, then cell apoptosis and protein expression were measured as described in “Materials and methods.” Error bars represent the S.E.M. for 3 independent experiments; *P < .01. (F) Cells were treated with 5 μM 3-AP for 24 hours, then DNA damage was evaluated by using the CometAssay.