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

Long Fang1,2, Ruofei Zhang2, Lin Shi3

  • 1Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 100049, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|October 27, 2023
PubMed

Insights

Inorganic selenium, delivered via a nanomedicine, effectively treats t(8;21) leukemia by inducing cell differentiation. This epigenetic drug targets the AML1-ETO oncoprotein, offering a promising new therapy for leukemia.

Area of Science:

  • Biomedical Engineering
  • Oncology
  • Nanomedicine

Background:

  • Arsenic's success against PML-RARα oncoprotein highlights inorganic compounds' anti-leukemia potential.
  • Inorganic selenium shows promise in solid tumors and is explored for t(8;21) leukemia therapy.

Purpose of the Study:

  • To investigate the therapeutic effect of inorganic selenium on t(8;21) leukemia.
  • To develop and evaluate a leukemia-targeting selenium nanomedicine as an epigenetic drug.

Main Methods:

  • A selenium nanomedicine was constructed using a bioengineered protein nanocage.
  • The nanomedicine's effect on t(8;21) leukemia cell differentiation was assessed.
  • Mechanistic studies analyzed selenium metabolism, histone deacetylase inhibition, and oncoprotein degradation.

Main Results:

  • The selenium nanomedicine significantly induced differentiation of t(8;21) leukemia cells into mature myeloid cells.
  • Selenium inhibited histone deacetylases, leading to AML1-ETO oncoprotein degradation.
  • Key myeloid differentiation factors (PU.1, C/EBPα) increased, while C-KIT decreased.

Conclusions:

  • Protein-nanocaged selenium acts as an effective epigenetic drug against t(8;21) leukemia.
  • The nanomedicine induces leukemia cell differentiation by regulating AML1-ETO.
  • This selenium-based therapy shows potential for treating t(8;21) leukemia.
Keywords:
AML1-ETOoncoprotein degradationprotein nanocageselenium nanoparticlet(8;21) leukemia

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