Reversine-Induced Telomere Architecture Remodeling in Chronic Myeloid Leukemia Cell Lines: Insights from TeloView®

Fábio Morato de Oliveira1, Isabela Dias Cruvinel1, Bruno Machado Rezende Ferreira1

  • 1Laboratory of Human and Medical Genetics, Federal University of Jataí, Jataí 75801-615, Goiás, Brazil.

PubMed

Insights

Reversine triggers apoptosis and remodels telomeres in chronic myeloid leukemia (CML) cells by inhibiting Aurora kinases. This study reveals its dual action on genomic stability and nuclear organization, suggesting therapeutic potential.

Area of Science:

  • * Oncology
  • * Molecular Biology
  • * Genetics

Background:

  • * Reversine, an Aurora kinase inhibitor, is known for inducing apoptosis and chromatin remodeling.
  • * Its effects on telomere dynamics and nuclear organization in chronic myeloid leukemia (CML) are not well understood.
  • * Investigating these effects is crucial for understanding CML pathogenesis and therapeutic strategies.

Purpose of the Study:

  • * To investigate the impact of reversine on telomere architecture, genomic instability, and apoptosis in K-562 and MEG-01 CML cell lines.
  • * To elucidate the mechanisms by which reversine affects nuclear organization and cell viability in CML.

Main Methods:

  • * Cytotoxicity assessed via caspase-3/7 activation assays.
  • * Quantitative PCR used to measure AURKA and AURKB mRNA expression.
  • * Three-dimensional telomere architecture analyzed using TeloView software after Q-FISH labeling.

Main Results:

  • * Reversine induced dose- and time-dependent apoptosis and downregulated AURKA/AURKB expression.
  • * 3D telomere analysis showed reduced telomere number, signal intensity, and nuclear volume, indicating reorganization rather than instability.
  • * Observed nuclear remodeling and apoptotic commitment suggest a dual mechanism of action.

Conclusions:

  • * Reversine modulates CML cell genomic stability through Aurora kinase inhibition and telomere remodeling.
  • * 3D telomere profiling reveals reversine's potential in targeting nuclear disorganization and mitotic dysregulation in leukemia.
  • * Findings highlight reversine as a potential therapeutic agent for CML.

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