Reversine-Induced Telomere Architecture Remodeling in Chronic Myeloid Leukemia Cells: Insights from TeloView® Analysis of 3D Nuclear Architecture
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Reversine, a synthetic purine analog, has been recognized for its dual role in cellular dedifferentiation and inhibition of mitotic kinases, particularly aurora A and B. Chronic myeloid leukemia (CML) cells exhibit genomic instability associated with dysregulated telomere dynamics. This study investigates the effects of reversine on three-dimensional (3D) telomere architecture of CML cell lines (K-562 and MEG-01), using TeloView® analysis. Our findings demonstrate that reversine treatment significantly alters already dynamically changed 3D telomere organization in CML, reducing the total number of telomeres, telomere aggregates, and nuclear volume while decreasing the expression of AURKA and AURKB. These changes suggest a potential mechanism by which reversine impacts chromatin integrity and leukemic cell viability, namely through the pronounced modulation of 3D telomere architecture. The telomere-dependent destablization of the 3D genome may contribute to reversine’s anti-leukemic effects leading to impaired mitotic progression. Our results support further exploration of reversine as a potential therapeutic agent in CML, particularly in combination with current treatment strategies targeting telomere and chromatin dynamics.