We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- 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
Wang, Hao; Liu, Yu-chen; Zhu, Cheng-ying; Yan, Fei; Wang, Meng-zhen; Chen, Xiao-su; Wang, Xiao-kai; Pang, Bao-xu; Li, Yong-hui; Liu, Dai-hong; Gao, Chun-ji; Liu, Shu-jun; Dou, Li-ping
- 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.
- Subjects
ACUTE myeloid leukemia; ANTHRACYCLINES; HISTONE deacetylase inhibitors; CYTARABINE; DISEASE relapse; SALVAGE therapy
- Publication
Journal of Experimental & Clinical Cancer Research (17569966), 2020, Vol 39, Issue 1, p1
- ISSN
1756-9966
- Publication type
Article
- DOI
10.1186/s13046-020-01792-8