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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.
Abstract:
Reversine is a small-molecule Aurora kinase inhibitor known for its pro-apoptotic effects and potential to remodel chromatin architecture. Although its impact on mitotic regulation is established, its effects on telomere dynamics and nuclear organization in chronic myeloid leukemia (CML) remain unclear. This study aimed to investigate the effects of reversine on telomere architecture, genomic instability, and apoptosis in CML cell lines (K-562 and MEG-01). Reversine was applied at increasing concentrations, and cytotoxicity was assessed using caspase-3/7 activation assays. Quantitative PCR was used to measure AURKA and AURKB mRNA expressions. Three-dimensional telomere architecture was analyzed with TeloView® v1.03 software after Q-FISH labeling to quantify telomere number, signal intensity, aggregation, nuclear volume, and a/c ratio. Reversine induced a dose- and time-dependent apoptotic response in both cell lines and significantly downregulated AURKA and AURKB expressions. Three-dimensional telomere analysis revealed a marked reduction in telomere number and aggregates, signal intensity, and nuclear volume. While reduced signal intensity may indicate telomere shortening, the concurrent decrease in aggregation and altered spatial parameters suggests telomeric reorganization rather than progressive instability. These features reflect structural nuclear remodeling and early apoptotic commitment. Differences between K-562 and MEG-01 responses underscore potential heterogeneity in telomere maintenance mechanisms. Reversine modulates genomic stability in CML cells through dual mechanisms involving Aurora kinase inhibition and telomere architecture remodeling. The integration of 3D telomere profiling highlights reversine's potential as a therapeutic agent targeting nuclear disorganization and mitotic dysregulation in leukemia.
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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