CLL cell kill by MDM2 inhibitors is independent of IgV-mutation status or ZAP-70 expression but dependent on the presence of del17p. CLL samples (n=106) were enriched for CD19⁺ cells through negative selection and incubated for 36 hours with various concentrations of either MI-63 or Nutlin3. Samples were prepared for annexin-V and PI staining and analyzed by flow cytometry, and the residual live and nonapoptotic cell fraction was calculated for each concentration through comparison with the untreated control incubation. (A) MI-63 assay results, composites, excluding cases with p53 aberrations. Red indicates the IgV_H-mutated CLL group; black, the IgV_H-unmutated CLL group. (B) Nutlin3 assay results, composites, excluding cases with p53 aberrations. Red indicates the IgV_H-mutated CLL group; black, the IgV_H-unmutated CLL group. (C) MI-63 assay results, composites, excluding cases with p53 aberrations. Red indicates the ZAP-70–negative CLL group; black, the ZAP-70–positive CLL group. (D) Nutlin3 assay results, composites, excluding cases with p53 aberrations. Red indicates the ZAP-70–negative CLL group; black, the ZAP-70–positive CLL group. (E) MI-63 assay results, composites, including cases with p53 aberrations; various hierarchical FISH categories are indicated. (F) Nutlin3 assay results, composites, including cases with p53 aberrations; various hierarchical FISH categories are indicated. Standard deviations are indicated by vertical black bars. Results are displayed as the mean plus or minus one standard deviation, with an asterisk to denote the comparisons that were significant at the P ≤ .001 level.