Abstract
Ibrutinib, an inhibitor of Bruton's tyrosine kinase(BTK), has shown promising pharmacologic effects in acute myeloid leukemia (AML). In this study, we report that AC0010 as a novel BTK inhibitor inhibits the cell proliferation, reduces colony-forming capacity, induces cell apoptosis and arrests cell cycle in AML cells, especially in those carrying FLT3 mutations. Surprisingly, AC0010 is found more sensitive than ibrutinib in treating AML. Mechanically, we showed that AC0010 not only targeting the phosphorylation of BTK, but also the crucial PI3K survival pathway. Furthermore, we observed that AC0010 could also suppress the expression of p-FLT3 and downstream target p-STAT5 in AML cells with FLT3 mutations. Moreover, our in vitro and in vivo data clarify that AC0010 can synergize with Homoharringtonine (HHT), a natural plant alkaloid, in treating AML with or without FLT3-ITD mutations. Collectively, our results suggest that AC0010 might be a promising drug in treating AML patients, and synergizes the efficiency of Homoharringtonine in AML.
Jin:College of Medicine, Zhejiang University: Employment; The National Natural Science Foundation of China: Research Funding.
Author notes
Asterisk with author names denotes non-ASH members.
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