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• Research Paper Volume 12, Issue 16 pp 16083-16098

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

  Relevance score: 7.3616304

  Yi-Lin Kong, Bi-Hui Pan, Jin-Hua Liang, Hua-Yuan Zhu, Li Wang, Yi Xia, Jia-Zhu Wu, Lei Fan, Jian-Yong Li, Wei Xu

  Keywords: chronic lymphocytic leukemia, autophagy, chidamide, histone deacetylase inhibitor

  Published in Aging on August 27, 2020

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  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.