Fig. 2
JNK inhibition reduces viability of Ph+ B-ALL cells. a Levels of phosphorylated and total JNK and c-JUN in SUP-B15 cells transduced with lentivirus vectors containing control shRNA (ShNC), shRNA targeting JNK (ShJNK#1), or ShJNK#2 were detected by western blot analysis with antibodies indicated. Actin was used as a loading control. b Proliferation of SUP-B15 cells expressing control and JNK shRNA were plotted by counting viable cells over a period of 3 days. c SUP-B15 cells were treated with JNK inhibitor JNK-IN-8 or SP600125 for 12 h, followed by western blot analysis using antibodies against phosphorylated and total c-JUN. d, e Viability of SUP-B15 and a CML blast crisis cell line K562 cells treated with various concentrations of JNK-IN-8 (d) or SP600125 (e) for 48 h was measured by the CellTiter Glo assay. Normalized cell proliferation was presented and compound’s IC50 value calculated. f, g Viability of CD19+ B lymphocytes isolated from normal and BCR/ABLp190 bone marrow transduction and transplantation mice treated with various concentrations of JNK-IN-8 (f) or SP600125 (g) for 48 h was measured by the CellTiter Glo assay. Normalized cell proliferation was presented and compound’s IC50 value calculated. h The nucleated bone marrow cells (NBMC) from a healthy donor and primary BM cells isolated from 6 patients with Ph+ B-ALL were treated with different concentrations of JNK-IN-8 for 48 h. Cell viability was measured by the CellTiter Glo assay. Data are presented as mean ± SD, and P values were calculated using Student’s t test. *P < 0.05, **P < 0.01, and ***P < 0.001