Chidamide increases the sensitivity of refractory or relapsed acute myeloid leukemia cells to anthracyclines via regulat
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(2020) 39:278
RESEARCH
Open Access
Chidamide increases the sensitivity of refractory or relapsed acute myeloid leukemia cells to anthracyclines via regulation of the HDAC3 -AKT-P21-CDK2 signaling pathway Hao Wang1†, Yu-chen Liu1†, Cheng-ying Zhu1†, Fei Yan2, Meng-zhen Wang1, Xiao-su Chen3, Xiao-kai Wang4, Bao-xu Pang5, Yong-hui Li1, Dai-hong Liu1*, Chun-ji Gao1*, Shu-jun Liu6* and Li-ping Dou1*
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. (Continued on next page)
* Correspondence: [email protected]; [email protected]; [email protected]; [email protected] † Hao Wang, Yu-chen Liu and Cheng-ying Zhu contributed equally to this work. 1 Department of Hematology, Chinese People’s Liberation Army (PLA) General Hospital, 28 Fuxing Road, Beijing 100853, China 6 The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, v
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