髓系白血病
体内
离体
癌症研究
移植
医学
造血
造血干细胞移植
细胞培养
药理学
细胞生物学
白血病
生物
干细胞
免疫学
内科学
生物技术
遗传学
作者
Sheng Bi,Kai Chen,Lin Feng,Gang Fu,Qianying Yang,Manman Deng,Haijun Zhao,Zhifeng Li,Lian Yu,Zhihong Fang,Bing Xu
标识
DOI:10.1016/j.ejphar.2019.05.020
摘要
Acute myeloid leukemia (AML) is a heterogeneous malignancy of hematopoietic stem cells with poor clinical outcome despite recent improvements in chemotherapy and stem cell transplantation regimens. Thus, new therapeutic agents are urgently needed in order to prolong the disease-free survival of AML patients in clinic. Here, we report that BBI608 is highly active against diverse AML cell lines in vitro and primary samples obtained from patients with AML ex vivo, as well as effective in vivo in AML xenograft models. Meanwhile, the anti-AML property of BBI608 is closely associated with the inhibition of Stat3 pathway and induction of DNA damage. Of note, BBI608 combined with Bcl-2 inhibitor (i.e., ABT-199) exerts a significantly enhanced anti-leukemia effect in BBI608-resistant cell line Kasumi-1. Together, the present findings suggest that BBI608 might represent a potential candidate agent for AML treatment.
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