期刊
EUROPEAN JOURNAL OF HAEMATOLOGY
卷 92, 期 2, 页码 111-120出版社
WILEY
DOI: 10.1111/ejh.12202
关键词
rapamycin; imatinib; Ph plus acute lymphoblastic leukemia; mammalian target of rapamycin signaling pathway; autophagy
类别
资金
- National Natural Science Foundation of China [30770912]
- Foundation of the Science & Technology Department of Sichuan Province [2008SZ0017]
- National Science & Technology Pillar Program [2008BAI61B01]
BCR-ABL fusion gene typically causes a type of acute lymphoblastic leukemia (ALL), known as Ph+ ALL. Although imatinib (IM) treatment induced high rates of complete response (CR), serious acute and late complications are frequent, whereas more vexatiously resistance to chemotherapy and clinical relapse develops. Therefore, the efficacy of treatment in Ph+ ALL is still to be determined. In this study, we focused our attention on the potential benefit of rapamycin (RAPA), an mammalian target of rapamycin (mTOR) inhibitor, in combination with IM on a Ph+ ALL cell line SUP-B15 and a primary Ph+ ALL sample in vitro. Analysis of cell proliferation showed that RAPA (50nm) plus IM exerted good synergistic effect on Ph+ ALL cells. Notably, we found that IM treatment induced the abnormal activation of the components of mTOR signaling pathway and p-BCR-ABL, whereas RAPA potently eliminated this deleterious side effect induced by IM and might overcome the resistance to IM. The synergistic effect was also associated with the increase in autophagy, which seemed to have an opposite role with apoptosis in Ph+ ALL cells, and cell cycle arrest in G(1) phase. Altogether, our results suggested that IM in combination with RAPA was more effective for Ph+ ALL cells than IM alone.
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