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Short telomere length and its correlation with gene mutations in myelodysplastic syndrome

BACKGROUND: Telomere erosion can lead to genomic instability and cancer progression. It has been suggested that the shortest telomere, not the average telomere length (TL), is critical for cell viability. Some studies have shown shorter TL in myelodysplastic syndrome (MDS) patients but the criticall...

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Autores principales: Hwang, Sang Mee, Kim, Seon Young, Kim, Jung Ah, Park, Hee-Sue, Park, Si Nae, Im, Kyongok, Kim, Kwantae, Kim, Sung-Min, Lee, Dong Soon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964031/
https://www.ncbi.nlm.nih.gov/pubmed/27465399
http://dx.doi.org/10.1186/s13045-016-0287-9
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author Hwang, Sang Mee
Kim, Seon Young
Kim, Jung Ah
Park, Hee-Sue
Park, Si Nae
Im, Kyongok
Kim, Kwantae
Kim, Sung-Min
Lee, Dong Soon
author_facet Hwang, Sang Mee
Kim, Seon Young
Kim, Jung Ah
Park, Hee-Sue
Park, Si Nae
Im, Kyongok
Kim, Kwantae
Kim, Sung-Min
Lee, Dong Soon
author_sort Hwang, Sang Mee
collection PubMed
description BACKGROUND: Telomere erosion can lead to genomic instability and cancer progression. It has been suggested that the shortest telomere, not the average telomere length (TL), is critical for cell viability. Some studies have shown shorter TL in myelodysplastic syndrome (MDS) patients but the critically short telomeres, the variability of TL within individual patient has not been evaluated. Thus, we aimed to investigate the TL of MDS patients and assessed the association of TL with recurrent genetic mutations in MDS. METHODS: We measured the TL of bone marrow nucleated cells for diagnostic samples at a single-cell level by quantitative fluorescence in situ hybridization (Q-FISH) for 58 MDS patients and analyzed the minimum, median, average, standard deviation, average of the 0th to 10th percentile TL within a patient, and the proportion of cells with TL that is shorter than the lowest 10th percentile of the normal control (NC). The correlations of TL to clinical parameters, cytogenetic results, and genetic mutations were assessed. RESULTS: MDS patients showed eroded telomeres and narrow distribution compared to the NC (P < 0.001, P = 0.018, respectively). Patients with mutation showed significantly lesser cells with short TL, below the lowest 10th percentile of the NC (P = 0.017), but no differences in TL were found according to mutations/cytogenetic abnormalities except for CSF3R mutation. However, those patients with a high percentage (≥80 %) of cells with short TL showed poorer overall survival (P = 0.021), and this was an independent prognostic factor, along with TP53, U2AF1 mutation, and high BM blast count (P = 0.044, 0.001, 0.004, 0.012, respectively). CONCLUSIONS: The shortest TL, which determines the fate of the cell, was significantly shorter, and higher burden of cells with short TL were found in MDS, which correlated with poor survival, suggesting the need to measure TL in single cells by Q-FISH. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13045-016-0287-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-49640312016-07-29 Short telomere length and its correlation with gene mutations in myelodysplastic syndrome Hwang, Sang Mee Kim, Seon Young Kim, Jung Ah Park, Hee-Sue Park, Si Nae Im, Kyongok Kim, Kwantae Kim, Sung-Min Lee, Dong Soon J Hematol Oncol Research BACKGROUND: Telomere erosion can lead to genomic instability and cancer progression. It has been suggested that the shortest telomere, not the average telomere length (TL), is critical for cell viability. Some studies have shown shorter TL in myelodysplastic syndrome (MDS) patients but the critically short telomeres, the variability of TL within individual patient has not been evaluated. Thus, we aimed to investigate the TL of MDS patients and assessed the association of TL with recurrent genetic mutations in MDS. METHODS: We measured the TL of bone marrow nucleated cells for diagnostic samples at a single-cell level by quantitative fluorescence in situ hybridization (Q-FISH) for 58 MDS patients and analyzed the minimum, median, average, standard deviation, average of the 0th to 10th percentile TL within a patient, and the proportion of cells with TL that is shorter than the lowest 10th percentile of the normal control (NC). The correlations of TL to clinical parameters, cytogenetic results, and genetic mutations were assessed. RESULTS: MDS patients showed eroded telomeres and narrow distribution compared to the NC (P < 0.001, P = 0.018, respectively). Patients with mutation showed significantly lesser cells with short TL, below the lowest 10th percentile of the NC (P = 0.017), but no differences in TL were found according to mutations/cytogenetic abnormalities except for CSF3R mutation. However, those patients with a high percentage (≥80 %) of cells with short TL showed poorer overall survival (P = 0.021), and this was an independent prognostic factor, along with TP53, U2AF1 mutation, and high BM blast count (P = 0.044, 0.001, 0.004, 0.012, respectively). CONCLUSIONS: The shortest TL, which determines the fate of the cell, was significantly shorter, and higher burden of cells with short TL were found in MDS, which correlated with poor survival, suggesting the need to measure TL in single cells by Q-FISH. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13045-016-0287-9) contains supplementary material, which is available to authorized users. BioMed Central 2016-07-28 /pmc/articles/PMC4964031/ /pubmed/27465399 http://dx.doi.org/10.1186/s13045-016-0287-9 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Hwang, Sang Mee
Kim, Seon Young
Kim, Jung Ah
Park, Hee-Sue
Park, Si Nae
Im, Kyongok
Kim, Kwantae
Kim, Sung-Min
Lee, Dong Soon
Short telomere length and its correlation with gene mutations in myelodysplastic syndrome
title Short telomere length and its correlation with gene mutations in myelodysplastic syndrome
title_full Short telomere length and its correlation with gene mutations in myelodysplastic syndrome
title_fullStr Short telomere length and its correlation with gene mutations in myelodysplastic syndrome
title_full_unstemmed Short telomere length and its correlation with gene mutations in myelodysplastic syndrome
title_short Short telomere length and its correlation with gene mutations in myelodysplastic syndrome
title_sort short telomere length and its correlation with gene mutations in myelodysplastic syndrome
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964031/
https://www.ncbi.nlm.nih.gov/pubmed/27465399
http://dx.doi.org/10.1186/s13045-016-0287-9
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