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Journal of Experimental & Clinical Cancer Research

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01-12-2020 | Acute Myeloid Leukemia | Research

Chidamide increases the sensitivity of refractory or relapsed acute myeloid leukemia cells to anthracyclines via regulation of the HDAC3 -AKT-P21-CDK2 signaling pathway

Authors: Hao Wang, Yu-chen Liu, Cheng-ying Zhu, Fei Yan, Meng-zhen Wang, Xiao-su Chen, Xiao-kai Wang, Bao-xu Pang, Yong-hui Li, Dai-hong Liu, Chun-ji Gao, Shu-jun Liu, Li-ping Dou

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2020

Abstract

Background

Induction therapy for acute myeloid leukemia (AML) is an anthracycline-based chemotherapy regimen. However, many patients experience a relapse or exhibit refractory disease (R/R). There is an urgent need for more effective regimens to reverse anthracycline resistance in these patients.

Methods

In this paper, Twenty-seven R/R AML patients with anthracycline resistance consecutively received chidamide in combination with anthracycline-based regimen as salvage therapy at the Chinese PLA General Hospital.

Results

Of the 27 patients who had received one course of salvage therapy, 13 achieved a complete response and 1 achieved a partial response. We found that the HDAC3-AKT-P21-CDK2 signaling pathway was significantly upregulated in anthracycline-resistant AML cells compared to non-resistant cells. AML patients with higher levels of HDAC3 had lower event-free survival (EFS) and overall survival (OS) rates. Moreover, anthracycline-resistant AML cells are susceptible to chidamide, a histone deacetylase inhibitor which can inhibit cell proliferation, increase cell apoptosis and induce cell-cycle arrest in a time- and dose-dependent manner. Chidamide increases the sensitivity of anthracycline-resistant cells to anthracycline drugs, and these effects are associated with the inhibition of the HDAC3-AKT-P21-CDK2 signaling pathway.

Conclusion

Chidamide can increase anthracycline drug sensitivity by inhibiting HDAC3-AKT-P21-CDK2 signaling pathway, thus demonstrating the potential for application.

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Title: Chidamide increases the sensitivity of refractory or relapsed acute myeloid leukemia cells to anthracyclines via regulation of the HDAC3 -AKT-P21-CDK2 signaling pathway
Authors: Hao Wang
Yu-chen Liu
Cheng-ying Zhu
Fei Yan
Meng-zhen Wang
Xiao-su Chen
Xiao-kai Wang
Bao-xu Pang
Yong-hui Li
Dai-hong Liu
Chun-ji Gao
Shu-jun Liu
Li-ping Dou
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Acute Myeloid Leukemia
Anthracycline
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2020
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-020-01792-8

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Abstract

Background

Methods

Results

Conclusion

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