Influence of ATM inhibition and ibrutinib on cell death in CLL or normal B cells. (A) Western blot showing the effects of the ATMis on pATM and pKAP1 and inhibition of pBTK by ibrutinib. Cells were treated for 24 hours in serum-free media (SFM). (B) Survival curves for ibrutinib and the ATMis against CLL and normal B cells, incubated for 24 hours in SFM or with anti-IgM. Cytotoxicity was measured by annexin V/7-aminoactinomycin D staining and flow cytometry. (C) Effective concentration to reduce cell survival by 50% (EC₅₀) for the ATMis and ibrutinib after incubating CLL cells in SFM and with anti-IgM for 24 hours. (D) Correlation between the cytotoxicities of the ATMis and ibrutinib in CLL cells. Data derived from panel C. (E) Comparison of the EC₅₀s in non-del11q and del11q (>50% cells with deletion) CLL samples. (F) Combenefit synergy plots of CLL cells incubated in SFM or with anti-IgM and exposed to chlorambucil (CLB) and AZD1390 or M3814 for 72 hours. (G) Combenefit synergy plots of CLL cells incubated in SFM or anti-IgM and exposed to ibrutinib and AZD1390 for 24 or 72 hours. (H) Western blot of del11q and non-del11q samples incubated for 24 hours with anti-IgM and treated with CLB and AZD1390 (ATMi), M3814 (DNA-PKi), or both. DMSO, dimethyl sulfoxide; ns, not significant.