Fig. 4. KPT-330 exhibited anti-leukemic effect on primary IM-resistant CML in CRM1-dependent manner.

a Sequencing data showed primary CML cells without (IM- Sensitive) or with ABL T315I mutation. b Western blot showed CRM1 protein were highly expressed in the primary CML cells, especially in the T315I-mutated cells. IM-sensitive CML was treated with 0.1 nM KPT-330 and IM-Resistant (with or without T315I mutation) CML with 1.3 nM KPT-330, respectively. c KPT-330 inhibited primary CML growth in time-dependent manner. Apoptosis was induced not only in IM-sensitive, but also in IM-Resistant (with or without T315I mutation) CML cells after KPT-330 treatment for 48 h (d, e). f Exposure to KPT-330 for 48 h significantly reduced CRM1 expression in primary CML as shown by western blot. ◊ compared with control, P < 0.05, Student’s t-test. Data were expressed as mean ± SD. Shown were representative data of 3 independent experiments