伊布替尼
高三尖杉酯碱
髓系白血病
布鲁顿酪氨酸激酶
癌症研究
Fms样酪氨酸激酶3
白血病
米多司他林
药理学
医学
生物
酪氨酸激酶
突变
免疫学
内科学
慢性淋巴细胞白血病
受体
生物化学
基因
作者
Xia Li,Xiufeng Yin,Huafeng Wang,Jiansong Huang,Mengxia Yu,Zeyu Ma,Chenying Li,Yile Zhou,Xiao Yan,Shujuan Huang,Jie Jin
出处
期刊:Blood
[American Society of Hematology]
日期:2016-12-02
卷期号:128 (22): 5225-5225
标识
DOI:10.1182/blood.v128.22.5225.5225
摘要
Abstract Acute myeloid leukemia (AML) is a highly heterogenous disease and the patients with an internal tandem duplication mutation in FMS-liketyrosine-kinase-3 (FLT3-ITD) have a negative impact on outcome. Finding effective treatment regimens is desperately needed. In this study, we explored the inhibitory effects and mechanism of homoharringtonine (HHT) in combination with ibrutinib on FLT3-ITD mutant AML cells. Consequently, we observed a synergistic inhibitory effect when ibrutinib was combined with HHT to inhibit cell proliferation, induce apoptosis and arrest cell cycle at G0/G1 phase in MV4-11 and MOLM-13 leukemia cells. Our results indicate that the mechanisms of the combination effect are mainly via regulating the STAT5/Pim-2/C-Myc pathway, AKT pathway and Bcl-2 family, activation p21WAF1/CIP1 and inhibiting CCND/CDK complex protein. Interestingly, synergistic cytotoxicity of ibrutinib and HHT was both dependent of FLT3 and BTK. Here we provide a novel effective therapeutic approach for the treatment of AML patients with FLT3-ITD mutation. Disclosures No relevant conflicts of interest to declare.
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