Figure 7

Analysis of DDR in CyclinA2+ and CyclinA2- cells demonstrates cell-cycle specific effects of individual genotoxins in AML samples. Primary AML (PBMC and BMMC) samples were treated with etoposide (30 μg/mL), PARP inhibitor AZD2281 (6 μg/mL), temozolomide (10 μg/mL), or the combination of AZD2281 + temozolomide (6 μg/mL + 10 μg/mL) for 6 hr. (A) Example flow plots of CyclinA2 vs. p-H2AX for all leukemic cells of a representative AML sample. (B) Shown is the proportion of cells (Uu metric) with induced p-H2AX in each sample; this metric allows comparisons of induced DDR from different drugs on a normalized scale. Modulated signaling through p-H2AX was measured in the bulk leukemic cell population (All cells) or in CyclinA2- or CyclinA2+ subsets. Tabulated below are the average values of all AML samples in each population.