CI values for doxorubicin, prednisone, and methotrexate (at the LD50 dose) in combination with the hERG1 inhibitor E4031 (at both 20μM and 5μM) in 697 and primary BCP-ALL cells, BCP-ALL(4) and BCP-ALL(3), cultured with or without MSCs (suspension)*
| . | Suspension . | P (suspension vs MSC) . | ΜSC . | P (E4031 20μM vs E4031 5μM) . |
|---|---|---|---|---|
| 697 cell line | ||||
| Doxorubicin + E4031 20μM | > 1 | 0.002 | 0.368 ± 0.037 | 0.039 |
| Doxorubicin + E4031 5μM | 0.605 ± 0.082 | 0.037 | 0.294 ± 0.020 | |
| Prednisone + E4031 20μM | > 1 | 0.041 | 0.722 ± 0.112 | 0.002 |
| Prednisone + E4031 5μM | 0.887 ± 0.103 | 0.0001 | 0.298 ± 0.075 | |
| Methotrexate + E4031 20μM | > 1 | 0.003 | 0.317 ± 0.081 | 0.021 |
| Methotrexate + E4031 5μM | 0.563 ± 0.096 | 0.023 | 0.224 ± 0.076 | |
| BCP-ALL (4) | ||||
| Doxorubicin + E4031 20μM | > 1 | 0.008 | 0.679 ± 0.087 | 0.003 |
| Doxorubicin + E4031 5μM | > 1 | 0.001 | 0.345 ± 0.033 | |
| Prednisone + E4031 20μM | > 1 | > 1 | 0.042 | |
| Prednisone + E4031 5μM | > 1 | 0.043 | 0.854 ± 0.096 | |
| Methotrexate + E4031 20μM | > 1 | 0.002 | 0.446 ± 0.081 | 0.022 |
| Methotrexate + E4031 5μM | > 1 | 0.000 | 0.203 ± 0.073 | |
| BCP-ALL (3) | ||||
| Doxorubicin + E4031 20μM | 0.865 ± 0.105 | 0.036 | 0.487 ± 0.086 | 0.031 |
| Doxorubicin + E4031 5μM | 0.824 ± 0.043 | 0.025 | 0.398 ± 0.075 | |
| Prednisone + E4031 20μM | > 1 | > 1 | 0.004 | |
| Prednisone + E4031 5μM | > 1 | 0.037 | 0.876 ± 0.056 | |
| Methotrexate + E4031 20μM | > 1 | 0.005 | 0.865 ± 0.056 | |
| Methotrexate + E4031 5μM | > 1 | 0.033 | 0.849 ± 0.021 |
| . | Suspension . | P (suspension vs MSC) . | ΜSC . | P (E4031 20μM vs E4031 5μM) . |
|---|---|---|---|---|
| 697 cell line | ||||
| Doxorubicin + E4031 20μM | > 1 | 0.002 | 0.368 ± 0.037 | 0.039 |
| Doxorubicin + E4031 5μM | 0.605 ± 0.082 | 0.037 | 0.294 ± 0.020 | |
| Prednisone + E4031 20μM | > 1 | 0.041 | 0.722 ± 0.112 | 0.002 |
| Prednisone + E4031 5μM | 0.887 ± 0.103 | 0.0001 | 0.298 ± 0.075 | |
| Methotrexate + E4031 20μM | > 1 | 0.003 | 0.317 ± 0.081 | 0.021 |
| Methotrexate + E4031 5μM | 0.563 ± 0.096 | 0.023 | 0.224 ± 0.076 | |
| BCP-ALL (4) | ||||
| Doxorubicin + E4031 20μM | > 1 | 0.008 | 0.679 ± 0.087 | 0.003 |
| Doxorubicin + E4031 5μM | > 1 | 0.001 | 0.345 ± 0.033 | |
| Prednisone + E4031 20μM | > 1 | > 1 | 0.042 | |
| Prednisone + E4031 5μM | > 1 | 0.043 | 0.854 ± 0.096 | |
| Methotrexate + E4031 20μM | > 1 | 0.002 | 0.446 ± 0.081 | 0.022 |
| Methotrexate + E4031 5μM | > 1 | 0.000 | 0.203 ± 0.073 | |
| BCP-ALL (3) | ||||
| Doxorubicin + E4031 20μM | 0.865 ± 0.105 | 0.036 | 0.487 ± 0.086 | 0.031 |
| Doxorubicin + E4031 5μM | 0.824 ± 0.043 | 0.025 | 0.398 ± 0.075 | |
| Prednisone + E4031 20μM | > 1 | > 1 | 0.004 | |
| Prednisone + E4031 5μM | > 1 | 0.037 | 0.876 ± 0.056 | |
| Methotrexate + E4031 20μM | > 1 | 0.005 | 0.865 ± 0.056 | |
| Methotrexate + E4031 5μM | > 1 | 0.033 | 0.849 ± 0.021 |
Original data are from Figure 4 and supplemental Figure 7c. CI values were calculated using CalcuSyn software Version 2 (Biosoft). span lang=IT
CI > 1, antagonisms; CI = 1, additivity; CI < 1, synergy. The statistical analysis was performed using the Student t test comparing either CI values in suspension versus CI values on MSC, for each drug combination, or CI values in the presence of 20mM E4031 versus CI values in the presence of 5μM E4031. Only statistically significant P values are reported.