Oncotarget

Research Papers:

This article has been corrected. Correction in: Oncotarget. 2019; 10:6641-6642.

The combination effect of homoharringtonine and ibrutinib on FLT3-ITD mutant acute myeloid leukemia

Xia Li, Xiufeng Yin, Huafeng Wang, Jiansong Huang, Mengxia Yu, Zhixin Ma, Chenying Li, Yile Zhou, Xiao Yan, ShuJuan Huang and Jie Jin _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2017; 8:12764-12774. https://doi.org/10.18632/oncotarget.14463

Metrics: PDF 2543 views  |   HTML 3745 views  |   ?  


Abstract

Xia Li1,2,*, Xiufeng Yin1,2,*, Huafeng Wang1,2, Jiansong Huang1,2, Mengxia Yu1,2, Zhixin Ma1,2, Chenying Li1,2, Yile Zhou1,2, Xiao Yan1,2, ShuJuan Huang1,2, Jie Jin1,2,3

1Department of Hematology, The First Affiliated Hospital of Zhejiang University, Hangzhou, People’s Republic of China

2Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China

3Key Lab of Hematopoietic Malignancy, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China

*These authors contributed equally to this work and share first authorship

Correspondence to:

Jie Jin, email: [email protected]

Keywords: acute myeloid leukemia, FLT3-ITD, homoharringtonine, ibrutinib

Received: February 25, 2016     Accepted: December 25, 2016     Published: January 03, 2017

ABSTRACT

Acute myeloid leukemia (AML) is a highly heterogeneous disease and internal tandem duplication mutation in FMS-like tyrosine-kinase-3 (FLT3-ITD) has a negative impact on outcome. Finding effective treatment regimens is desperately needed. In this study, we explored the inhibitory effect 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, activating p21WAF1/CIP1 and inhibiting CCND/CDK complex protein. Interestingly, synergistic cytotoxicity of ibrutinib and HHT was dependent on both FLT3 and BTK. Here we provide a novel effective therapeutic approach for the treatment of AML patients with FLT3-ITD mutation.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 14463