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Open AccessArticle

3D Telomere Structure Analysis to Detect Genomic Instability and Cytogenetic Evolution in Myelodysplastic Syndromes

1
Cell Biology, Research Institute of Oncology and Hematology, The Genomic Centre for Cancer Research and Diagnosis, University of Manitoba, CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada
2
Arthur Siqueira Cavalcanti Hematology Institute (HEMORIO), Rio de Janeiro 20211-030, Brazil
3
Hospital das Clínicas, Universidade Federal do Paraná, Curitiba, Paraná 80060-240, Brazil
*
Author to whom correspondence should be addressed.
Cells 2019, 8(4), 304; https://doi.org/10.3390/cells8040304
Received: 5 March 2019 / Revised: 27 March 2019 / Accepted: 28 March 2019 / Published: 2 April 2019
(This article belongs to the Special Issue The Role of Telomere Biology in Aging and Human Disease)
The disease course of myelodysplastic syndromes (MDS) features chromosome instability and clonal evolution, leading to the sequential acquisition of novel cytogenetic aberrations and the accumulation of these abnormalities in the bone marrow. Although clonal cytogenetic abnormalities can be detected by conventional cytogenetics in 50% of patients with MDS, such distinguishing patterns are lacking in the other 50%. Despite the increase in the prognostic value of some biomarkers, none of them is specific and able to discriminate between stable and unstable patients that subsequently progress to acute myeloid leukemia. This pilot study aimed to investigate the potential use of the 3D telomere profiling to detect genomic instability in MDS patients with or without clonal cytogenetic evolution. The comparison between different time points in patients with cytogenetic changes showed that in the CD34+ MDS cells, there was a significant decrease in the total number of telomeric signals, the average intensity of signals and the total intensity of telomeres. By contrast, the number of aggregates increased during cytogenetic evolution (p < 0.001). This pattern was observed only for MDS patients with cytogenetic evolution but was absent in patients without cytogenetic changes. In conclusion, we demonstrated that the 3D nuclear telomere organization was significantly altered during the MDS disease course, and may have contributed to cytogenetic clonal evolution. View Full-Text
Keywords: myelodysplastic syndrome; cytogenetic evolution; genomic instability; 3D nuclear telomere organization myelodysplastic syndrome; cytogenetic evolution; genomic instability; 3D nuclear telomere organization
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Rangel-Pozzo, A.; de Souza, D.C.; Schmid-Braz, A.T.; Azambuja, A.P.; Ferraz-Aguiar, T.; Borgonovo, T.; Mai, S. 3D Telomere Structure Analysis to Detect Genomic Instability and Cytogenetic Evolution in Myelodysplastic Syndromes. Cells 2019, 8, 304.

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