Nutlin-3a efficiently induces p53-mediated apoptosis in CLL cells independent of Mdm2 or Atm expression levels. (A) High levels of Mdm2 were not associated with resistance to Nutlin-3a– or F-ara-A–induced apoptosis in CLL. Mdm2 protein expression levels relative to an internal control, β-actin, were determined in each sample and compared with normal bone marrow cells. (B) Low Atm levels did not prevent Nutlin-3a from inducing apoptosis in CLL. Atm protein expression levels relative to an internal control, β-actin, were determined in each sample, and compared with normal peripheral-blood lymphocytes. Although low Atm expression was associated with fludarabine resistance in 5 cases, these samples remained sensitive to Nutlin-induced apoptosis. Error bars indicate SEM.