STUDIUM ORGANIZACE CHROMATINU U CHRONICKÉ LYMFOCYTÁRNÍ LEUKEMIE

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Title in English Study of Chromatin Organization in Chronic Lymphocytic Leukemia
Authors

ČERNOVSKÁ Karolína PORC Jakub Paweł TAUŠOVÁ Kristýna ADAMOVÁ Sabina STRÁNSKÁ Kamila ONDROUŠKOVÁ Eva JAROŠOVÁ Marie PLEVOVÁ Karla

Year of publication 2024
Type Conference abstract
MU Faculty or unit

Central European Institute of Technology

Citation
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Description The spatial organization of chromatin is essential for fundamental cellular processes. Its hierarchical structure consists of compartments, topologically associated domains, and loops. Disruption of chromatin organization can lead to deregulation of cellular processes and promote tumor progression. Our aim was to describe the impact of chromatin reorganization in chronic lymphocytic leukemia (CLL), with a focus on patients with a complex karyotype (CK), which is associated with an unfavorable prognosis in CLL. Ten primary CLL samples with CK were analyzed using the Micro-C method to study chromatin conformation. Using bioinformatics tools, we assessed DNA interactions and characterized copy number variations (CNVs) and structural variants (SVs). The obtained results were evaluated in relation to both routine and research-based cytogenomic and sequencing methods. Additionally, we detected the formation of novel chromatin structures, which we correlated in selected samples with changes in gene expression determined by RNA sequencing. In all samples, we identified specific structural rearrangements and their impact on chromatin reorganization. Compared to other methods, Micro-C appears to be a reliable approach for detecting aberrations ?50 kb, particularly translocations. CNV profiles obtained using different methods were consistent. Furthermore, we observed the formation of new domains and loops as a consequence of SVs in all samples, which frequently correlated with changes in gene expression. The tumor genome undergoes extensive reorganization due to chromosomal rearrangements and alterations in chromatin interactions. Our research highlights the importance of studying chromatin conformation, which provides insights into the function and expression of the tumor genome and may help elucidate the biological and clinical manifestations of the disease. Hledat ChatG
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