2. Academic Validation
  3. Protein-Nanocaged Selenium Induces t(8;21) Leukemia Cell Differentiation via Epigenetic Regulation

Protein-Nanocaged Selenium Induces t(8;21) Leukemia Cell Differentiation via Epigenetic Regulation

  • Adv Sci (Weinh). 2023 Oct 27:e2300698. doi: 10.1002/advs.202300698.
Long Fang 1 2,  Ruofei Zhang 2,  Lin Shi 3,  Jiaying Xie 2,  Long Ma 2,  Yili Yang 4,  Xiyun Yan 2 5,  Kelong Fan 2 5
Affiliations

Affiliations

  • 1 Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 2 CAS Engineering Laboratory for Nanozyme, Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  • 3 Department of Hematology, Peking University International Hospital, Beijing, 102206, China.
  • 4 China Regional Research Centre, International Centre of Genetic Engineering and Biotechnology, Taizhou, 212200, China.
  • 5 Nanozyme Medical Center, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450052, China.
PMID: 37888866 DOI: 10.1002/advs.202300698
Abstract

The success of arsenic in degrading PML-RARα oncoprotein illustrates the great anti-leukemia value of inorganics. Inspired by this, the therapeutic effect of inorganic selenium on t(8; 21) leukemia is studied, which has shown promising anti-cancer effects on solid tumors. A leukemia-targeting selenium nanomedicine is rationally built with bioengineered protein nanocage and is demonstrated to be an effective epigenetic drug for inducing the differentiation of t(8;21) leukemia. The selenium drug significantly induces the differentiation of t(8;21) leukemia cells into more mature myeloid cells. Mechanistic analysis shows that the selenium is metabolized into bioactive forms in cells, which drives the degradation of the AML1-ETO oncoprotein by inhibiting histone deacetylases activity, resulting in the regulation of AML1-ETO target genes. The regulation results in a significant increase in the expression levels of myeloid differentiation transcription factors PU.1 and C/EBPα, and a significant decrease in the expression level of c-Kit protein, a member of the type III receptor tyrosine kinase family. This study demonstrates that this protein-nanocaged selenium is a potential therapeutic drug against t(8;21) leukemia through epigenetic regulation.

Keywords

AML1-ETO; oncoprotein degradation; protein nanocage; selenium nanoparticle; t(8;21) leukemia.

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