Background and purpose
The poor prognosis of acute megakaryoblastic leukaemia (AMKL) means there is a need to develop novel therapeutic
Purpose
The poor prognosis of acute megakaryoblastic leukaemia (AMKL) means there is a need to develop novel therapeutic
Results
A low dose of tetrandrine induced cell cycle arrest and megakaryocyte differentiation in AMKL cells via activation of autophagy. Molecularly, we demonstrated that this effect is mediated by activation of Notch1 and Akt and subsequent accumulation of ROS. In contrast, in normal mouse fetal liver cells, although tetrandrine induced autophagy, it did not affect cell proliferation or promote megakaryocyte differentiation, suggesting a specific effect of tetrandrine in malignant megakaryoblasts. Finally, tetrandrine also showed in vivo efficacy in an AMKL xenograft mouse model. Conclusions and implications: Modulating autophagy-mediated differentiation may be a novel strategy for treating AMKL, and tetrandrine has the potential to be developed as a differentiation-inducing agent for AMKL chemotherapy.