Reversine-Induced Telomere Architecture Remodeling in Chronic Myeloid Leukemia Cell Lines: Insights from TeloView® Analysis of 3D Nuclear Architecture

TL;DR

This study shows that reversine, a drug that inhibits Aurora kinases, can change telomere structure and induce cell death in chronic myeloid leukemia cells.

Contribution

The study reveals that reversine remodels telomere architecture and reduces genomic instability in CML cells through Aurora kinase inhibition.

Findings

Reversine induces apoptosis in CML cell lines in a dose- and time-dependent manner.

Reversine reduces telomere number, aggregation, and signal intensity, suggesting telomere reorganization.

Aurora kinase inhibition by reversine correlates with decreased genomic instability in CML cells.

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.

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