Effect of E4031 on chemotherapy-induced apoptosis in different culture conditions. The 697 cell line and a representative BCP-ALL primary sample (see also supplemental Figure 7) were cultured with or without MSCs (suspension) and exposed to LD50 doses of either doxorubicin (0.1 μg/mL), prednisone (5μM), or methotrexate (1.5μM), with or without the LD50 dose (20μM) or a subcytotoxic dose (5μM) of the hERG1 inhibitor E4031 for 48 hours. The percentage of annexin V+/propidium iodide− cells was measured. Values are means ± SD of 6 independent experiments (for the 697 cell line, 2 experiments for the BCP-ALL primary sample), each performed in quadruplicate (for the 697 cell line, in triplicate for the BCP-ALL primary sample). (A) 697 B-ALL cell line in the presence of 20μM E4031. (B) 697 B-ALL cell line in the presence of 5μM E4031. (C) BCP-ALL primary sample (case 4, see Figure 5 and supplemental Table 3) in the presence of 20μM E4031. (D) BCP-ALL primary sample (case 4, see Figure 5 and supplemental Table 3) in the presence of 5μM E4031. The values of the untreated controls are reported as dotted bars in each graph. Original values are: 697 (suspension): 3.5% ± 0.9% (n = 6); 697 (MSC): 2.8% ± 1% (n = 6); BCP-ALL(4; suspension): 11.1% ± 3.0% (n = 2); and BCP-ALL(4; MSC) 8.2% ± 2.9% (n = 2).
