Figure 3.

TP53/ATM WT CLL samples that were classified as ATM-dysfunctional display defective apoptotic responses to various DNA-damaging agents. (a, b) CLL cells of eight WT (nos. 6, 160, 647, 534, 854, 812, 912, 532) patients, which were classified as functional, and (a) four WT (nos. 13, 218, 190, 914) patients, which were classified as dysfunctional, and CLL cells of (b) five sole 11q deleted (nos. 785, 1023, 1072, 196, 270) patients, which were classified as p53/ATM-functional, and two sole 11q deleted (nos. 52, 825) patients, which were classified as ATM-dysfunctional, were treated with fludarabine or doxorubicin at increasing concentrations or irradiation (5 Gy). After 48 h, cell death was assessed by DIOC₆/PI staining and specific cell death was calculated as described in the Materials and Methods section. Presented is mean±S.E.M. Significant differences in response compared with functional WT CLL cells at the same concentration are presented as *0.01≤P<0.05; **0.001≤P<0.01; ***P<0.001 (Mann-Whitney U-test). (c) CD40L/Il21 activated CLL cells of n=2 functional, n=3 ATM dysfunctional and n=2 p53 dysfunctional CLL samples classified according to the RT-MLPA were treated with olaparib at increasing concentrations. After 3 days, cell death was assessed by DIOC₆/PI staining and specific cell death was calculated as described in the Materials and Methods section. Presented is mean±S.E.M.