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. 2021 Aug;39(4):961-970.
doi: 10.1007/s10637-021-01079-5. Epub 2021 Feb 10.

Histone deacetylase inhibitor chidamide regulates the Wnt/β-catenin pathway by MYCN/DKK3 in B-ALL

Linlin Zhao #  1 , Chengfang Lv #  2 , Lili Sun  3 , Qi Li  3 , Yuhuang Wang  3 , Min Wu  3 , Yuying Wang  3 , Zhibo Guo  3 , Sicheng Bian  3 , Desheng Kong  4 , Leilei Lin  3 , Yu Wang  3 , Jin Zhou  5 , Yinghua Li  6
Affiliations

Histone deacetylase inhibitor chidamide regulates the Wnt/β-catenin pathway by MYCN/DKK3 in B-ALL

Linlin Zhao et al. Invest New Drugs. 2021 Aug.

Abstract

Our previous studies revealed that MYCN downregulates the expression of DKK3, activates the Wnt/β-catenin signalling pathway at the transcriptional level, and thereby promotes the development of B cell acute lymphocytic leukaemia (B-ALL) but does not affect the methylation of the DKK3 promoter. Some studies have shown that MYCN is associated with histone acetylation. We speculate that histone deacetylase inhibitors (HDACis) can inhibit the Wnt/β-catenin signalling pathway by inhibiting MYCN and increasing the expression of DKK3. Based on previous experiments, we tested this hypothesis by analysing the changes in MYCN, DKK3 and the Wnt/β-catenin signalling pathways in B-ALL cells after treatment with the selective HDACi chidamide. The in vitro and in vivo experiments confirmed that chidamide inhibited the expression of MYCN and increased the expression of DKK3 by inhibiting the activity of histone deacetylase, and these effects resulted in inhibition of the Wnt/β-catenin signalling pathway and the proliferation of B-ALL cells. These findings indicate that chidamide might be used alone or in combination with other chemotherapy regimens for patients with B-ALL and thus provide a new approach to the treatment of B-ALL.

Keywords: B cell acute lymphocytic leukaemia; Chidamide; DKK3; MYCN; Wnt/β-catenin.

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