Figure 3.

AMG 900 can increase polyploidy, apoptosis, and p53 protein levels in AML cell lines, and can potentiate the activity of LDAC. A and B, U937 (TP53^MUT), HEL (TP53^MUT), GDM-1 (TP53^WT), and MOLM-13 (TP53^WT) cells were treated with AMG 900 at 33 nmol/L or DMSO for 48 hours. Western blot and cell-cycle analysis. A, Protein expression profiles of cl-caspase-3, total p53, p21, and β-actin. B, DNA content profiles with indicated Y-axis maximal (Y-max) count and ploidy (2N to 16N). C and D, AML cells treated with AMG 900, Ara-C, or DMSO, and in combination using 4 × 3 dose-matrix for 72 hours. Annexin-V apoptosis analysis. C, Representative scatter plots of annexin-V positivity percentages (red) for test agent alone and combined AMG 900 (4.0 nmol/L) and Ara-C (125 nmol/L). D, Percentage of annexin-V positivity across dose-matrix. E and F, MOLM-13 cells were treated with test agent alone at the indicated concentrations and in combination for 72 hours. Apoptosis and cell-cycle analysis. E, DNA content profiles with cl-caspase-3 positive population (red) with Y-max count and ploidy (2N to 16N). F, Percentage of total cell death (subG₁ + cl-capase-3) and ≥ 4N DNA content (mean ± SD).