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MDS shows a higher expression of hTERT and alternative splice variants in unactivated T-cells

Telomere instability and telomerase reactivation are believed to play an important role in the development of myelodysplastic syndromes (MDS). Abnormal enzymatic activity of human telomerase reverse transcriptase (hTERT), and its alternative splice variants have been reported to account for deregula...

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Autores principales: Dong, Wen, Wu, Lei, Sun, Houfang, Ren, Xiubao, Epling-Burnette, Pearlie K., Yang, Lili
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342131/
https://www.ncbi.nlm.nih.gov/pubmed/27655690
http://dx.doi.org/10.18632/oncotarget.12115
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author Dong, Wen
Wu, Lei
Sun, Houfang
Ren, Xiubao
Epling-Burnette, Pearlie K.
Yang, Lili
author_facet Dong, Wen
Wu, Lei
Sun, Houfang
Ren, Xiubao
Epling-Burnette, Pearlie K.
Yang, Lili
author_sort Dong, Wen
collection PubMed
description Telomere instability and telomerase reactivation are believed to play an important role in the development of myelodysplastic syndromes (MDS). Abnormal enzymatic activity of human telomerase reverse transcriptase (hTERT), and its alternative splice variants have been reported to account for deregulated telomerase function in many cancers. In this study, we aim to compare the differences in expression of hTERT and hTERT splice variants, as well as telomere length and telomerase activity in unstimulated T-cells between MDS subgroups and healthy controls. Telomere length in MDS cases was significantly shorter than controls (n = 20, p<0.001) and observed across all subtypes of MDS using World Health Organization classification (WHO subgroups versus control: RARS, p= 0.009; RCMD, p=0.0002; RAEB1/2, p=0.004, respectively) and the International Prognostic Scoring System (IPSS subgroups: Low+Int-1, p<0.001; Int-2+High, p=0.004). However, unstimulated T-cells from MDS patients (n=20) had significantly higher telomerase activity (p=0.002), higher total hTERT mRNA levels (p=0.001) and hTERT α+β- splice variant expression (p<0.001) compared to controls. Other hTERT splice variants were lower in expression and not significantly different among cases and controls. Telomerase activity was positively correlated with total hTERT levels in MDS (r=0.58, p=0.007). This data is in sharp contrast to data published previously by our group showing a reduction in telomerase and hTERT mRNA in MDS T-cells after activation. In conclusion, this study provides additional insight into hTERT transcript patterns and activity in peripheral T-cells of MDS patients. Additional studies are necessary to better understand the role of this pathway in MDS development and progression.
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spelling pubmed-53421312017-03-24 MDS shows a higher expression of hTERT and alternative splice variants in unactivated T-cells Dong, Wen Wu, Lei Sun, Houfang Ren, Xiubao Epling-Burnette, Pearlie K. Yang, Lili Oncotarget Research Paper Telomere instability and telomerase reactivation are believed to play an important role in the development of myelodysplastic syndromes (MDS). Abnormal enzymatic activity of human telomerase reverse transcriptase (hTERT), and its alternative splice variants have been reported to account for deregulated telomerase function in many cancers. In this study, we aim to compare the differences in expression of hTERT and hTERT splice variants, as well as telomere length and telomerase activity in unstimulated T-cells between MDS subgroups and healthy controls. Telomere length in MDS cases was significantly shorter than controls (n = 20, p<0.001) and observed across all subtypes of MDS using World Health Organization classification (WHO subgroups versus control: RARS, p= 0.009; RCMD, p=0.0002; RAEB1/2, p=0.004, respectively) and the International Prognostic Scoring System (IPSS subgroups: Low+Int-1, p<0.001; Int-2+High, p=0.004). However, unstimulated T-cells from MDS patients (n=20) had significantly higher telomerase activity (p=0.002), higher total hTERT mRNA levels (p=0.001) and hTERT α+β- splice variant expression (p<0.001) compared to controls. Other hTERT splice variants were lower in expression and not significantly different among cases and controls. Telomerase activity was positively correlated with total hTERT levels in MDS (r=0.58, p=0.007). This data is in sharp contrast to data published previously by our group showing a reduction in telomerase and hTERT mRNA in MDS T-cells after activation. In conclusion, this study provides additional insight into hTERT transcript patterns and activity in peripheral T-cells of MDS patients. Additional studies are necessary to better understand the role of this pathway in MDS development and progression. Impact Journals LLC 2016-09-19 /pmc/articles/PMC5342131/ /pubmed/27655690 http://dx.doi.org/10.18632/oncotarget.12115 Text en Copyright: © 2016 Dong et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Dong, Wen
Wu, Lei
Sun, Houfang
Ren, Xiubao
Epling-Burnette, Pearlie K.
Yang, Lili
MDS shows a higher expression of hTERT and alternative splice variants in unactivated T-cells
title MDS shows a higher expression of hTERT and alternative splice variants in unactivated T-cells
title_full MDS shows a higher expression of hTERT and alternative splice variants in unactivated T-cells
title_fullStr MDS shows a higher expression of hTERT and alternative splice variants in unactivated T-cells
title_full_unstemmed MDS shows a higher expression of hTERT and alternative splice variants in unactivated T-cells
title_short MDS shows a higher expression of hTERT and alternative splice variants in unactivated T-cells
title_sort mds shows a higher expression of htert and alternative splice variants in unactivated t-cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342131/
https://www.ncbi.nlm.nih.gov/pubmed/27655690
http://dx.doi.org/10.18632/oncotarget.12115
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