Three-dimensional nuclear telomere architecture and differential expression of aurora kinase genes in chronic myeloid leukemia to measure cell transformation
Abstract Background Telomere dysfunction results in aneuploidy, and ongoing chromosomal abnormalities. The three-dimensional (3D) nuclear organization of telomeres allows for a distinction between normal and tumor cells. On the other hand, aurora kinase genes (AURKA and AURKB) play an important role...
| Main Authors: | , , , , |
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| Format: | Article |
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BMC
2022-09-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-022-10094-5 |
| _version_ | 1818024708964089856 |
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| author | Fábio Morato de Oliveira Valderez Ravaglio Jamur Lismeri Wuicik Merfort Aline Rangel Pozzo Sabine Mai |
| author_facet | Fábio Morato de Oliveira Valderez Ravaglio Jamur Lismeri Wuicik Merfort Aline Rangel Pozzo Sabine Mai |
| author_sort | Fábio Morato de Oliveira |
| collection | DOAJ |
| description | Abstract Background Telomere dysfunction results in aneuploidy, and ongoing chromosomal abnormalities. The three-dimensional (3D) nuclear organization of telomeres allows for a distinction between normal and tumor cells. On the other hand, aurora kinase genes (AURKA and AURKB) play an important role regulating the cell cycle. A correlation between overexpression of aurora kinase genes and clinical aggressiveness has been demonstrated in different types of neoplasias. To better understand cellular and molecular mechanisms of CML evolution, it was examined telomere dysfunction (alterations in the 3D nuclear telomere architecture), and the expression levels of AURKA and AURKB genes in two clinical distinct subgroups of CML samples, from the same patient. Methods Eighteen CML patients, in total, 36 bone marrow samples (18 patients, chronic vs. accelerated/blast phase) were eligible for 3D telomeric investigations. Quantitative 3D imaging, cytologic diagnosis and cytogenetic determination of additional chromosomal abnormalities were assessed according to standard protocols. Results Using TeloView software, two CML subgroups were defined based on their 3D telomeric profiles, reflecting the different stages of the disease (chronic vs. accelerated/blast phase). Statistical analyses showed significant differences between the CML subgroups (p < 0.001). We also found that AURKA and AURKB mRNA were expressed at significantly higher levels in both CML subgroups, when compared with healthy donors. Our findings suggest that the evolution of CML progresses from a low to a high level of telomere dysfunction, that is, from an early stage to a more aggressive stage, followed by disease transformation, as demonstrated by telomere, additional chromosomal abnormalities, and gene expression profile dynamics. Conclusions Thus, we demonstrated that 3D telomere organization, in accordance with the genomic instability observed in CML samples were able to distinguish subgroup CML patients. Classifying CML patients based on these characteristics might represent an important strategy to define better therapeutic strategies. |
| first_indexed | 2024-12-10T04:04:31Z |
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| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-10T04:04:31Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-d69c5b2dfa6449fe93ebe14ac6881c702022-12-22T02:02:53ZengBMCBMC Cancer1471-24072022-09-0122111110.1186/s12885-022-10094-5Three-dimensional nuclear telomere architecture and differential expression of aurora kinase genes in chronic myeloid leukemia to measure cell transformationFábio Morato de Oliveira0Valderez Ravaglio Jamur1Lismeri Wuicik Merfort2Aline Rangel Pozzo3Sabine Mai4Laboratory of Medical Genetics, Câmpus Jatobá - Cidade Universitária, Federal University of JataíComplexo Hospital das Clínicas, Universidade Federal do ParanáComplexo Hospital das Clínicas, Universidade Federal do ParanáResearch Institute in Oncology and Hematology CancerCare Manitoba, The Genomic Centre for Cancer Research and Diagnosis, The University of ManitobaResearch Institute in Oncology and Hematology CancerCare Manitoba, The Genomic Centre for Cancer Research and Diagnosis, The University of ManitobaAbstract Background Telomere dysfunction results in aneuploidy, and ongoing chromosomal abnormalities. The three-dimensional (3D) nuclear organization of telomeres allows for a distinction between normal and tumor cells. On the other hand, aurora kinase genes (AURKA and AURKB) play an important role regulating the cell cycle. A correlation between overexpression of aurora kinase genes and clinical aggressiveness has been demonstrated in different types of neoplasias. To better understand cellular and molecular mechanisms of CML evolution, it was examined telomere dysfunction (alterations in the 3D nuclear telomere architecture), and the expression levels of AURKA and AURKB genes in two clinical distinct subgroups of CML samples, from the same patient. Methods Eighteen CML patients, in total, 36 bone marrow samples (18 patients, chronic vs. accelerated/blast phase) were eligible for 3D telomeric investigations. Quantitative 3D imaging, cytologic diagnosis and cytogenetic determination of additional chromosomal abnormalities were assessed according to standard protocols. Results Using TeloView software, two CML subgroups were defined based on their 3D telomeric profiles, reflecting the different stages of the disease (chronic vs. accelerated/blast phase). Statistical analyses showed significant differences between the CML subgroups (p < 0.001). We also found that AURKA and AURKB mRNA were expressed at significantly higher levels in both CML subgroups, when compared with healthy donors. Our findings suggest that the evolution of CML progresses from a low to a high level of telomere dysfunction, that is, from an early stage to a more aggressive stage, followed by disease transformation, as demonstrated by telomere, additional chromosomal abnormalities, and gene expression profile dynamics. Conclusions Thus, we demonstrated that 3D telomere organization, in accordance with the genomic instability observed in CML samples were able to distinguish subgroup CML patients. Classifying CML patients based on these characteristics might represent an important strategy to define better therapeutic strategies.https://doi.org/10.1186/s12885-022-10094-5CMLTelomereNuclear architectureGenomic instability |
| spellingShingle | Fábio Morato de Oliveira Valderez Ravaglio Jamur Lismeri Wuicik Merfort Aline Rangel Pozzo Sabine Mai Three-dimensional nuclear telomere architecture and differential expression of aurora kinase genes in chronic myeloid leukemia to measure cell transformation BMC Cancer CML Telomere Nuclear architecture Genomic instability |
| title | Three-dimensional nuclear telomere architecture and differential expression of aurora kinase genes in chronic myeloid leukemia to measure cell transformation |
| title_full | Three-dimensional nuclear telomere architecture and differential expression of aurora kinase genes in chronic myeloid leukemia to measure cell transformation |
| title_fullStr | Three-dimensional nuclear telomere architecture and differential expression of aurora kinase genes in chronic myeloid leukemia to measure cell transformation |
| title_full_unstemmed | Three-dimensional nuclear telomere architecture and differential expression of aurora kinase genes in chronic myeloid leukemia to measure cell transformation |
| title_short | Three-dimensional nuclear telomere architecture and differential expression of aurora kinase genes in chronic myeloid leukemia to measure cell transformation |
| title_sort | three dimensional nuclear telomere architecture and differential expression of aurora kinase genes in chronic myeloid leukemia to measure cell transformation |
| topic | CML Telomere Nuclear architecture Genomic instability |
| url | https://doi.org/10.1186/s12885-022-10094-5 |
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