Research Paper Volume 12, Issue 16 pp 16083—16098

Chidamide, a histone deacetylase inhibitor, inhibits autophagy and exhibits therapeutic implication in chronic lymphocytic leukemia

Yi-Lin Kong1,2,3, *, , Bi-Hui Pan1,2,3, *, , Jin-Hua Liang1,2,3, , Hua-Yuan Zhu1,2,3, , Li Wang1,2,3, , Yi Xia1,2,3, , Jia-Zhu Wu1,2,3, , Lei Fan1,2,3, , Jian-Yong Li1,2,3, , Wei Xu1,2,3, &, ,

  • 1 Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China
  • 2 Key Laboratory of Hematology of Nanjing Medical University, Nanjing 210029, China
  • 3 Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing 210029, China
* Equal contribution

Received: November 8, 2019       Accepted: June 4, 2020       Published: August 27, 2020
How to Cite

Copyright © 2020 Kong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Novel agents have made the management of chronic lymphocytic leukemia (CLL) more promising and personalized. However, long-term treatment is still warranted which may result in toxicity and resistance. Thus, new combination therapy may help achieve deeper remission and limited-duration therapy. Histone deacetylase inhibitors (HDACi) can affect many tumors by modulating key biological functions including autophagy. Studies have shown that some novel targeted agents including ibrutinib induce autophagy. This study aimed to explore the effect of oral HDAC inhibitor, chidamide, on CLL cells as well as the role of autophagy in this process. Here, we showed that autophagy flux in CLL cells was inhibited by chidamide via post-transcriptional modulation and chidamide had cytostatic and cytotoxic effects on CLL cells. Besides, the pro-survival role of autophagy in CLL cells was validated by using autophagy inhibitor and knocking down critical autophagy gene. Notably, a combination of chidamide and ibrutinib showed significant synergism and downregulated ibrutinib-induced autophagy. This work highlights the therapeutic potential of chidamide via its effect on autophagy, especially in combination with ibrutinib.


BTK: Bruton’s tyrosine kinase; CHI: chidamide; CHX: cycloheximide; CI: combination index; CLL: chronic lymphocytic leukemia; CQ: chloroquine; HDACi: histone deacetylase inhibitors; IB: ibrutinib; PTCL: peripheral T-cell lymphoma.