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Dysregulation of Telomere Lengths and Telomerase Activity in Myelodysplastic Syndrome

BACKGROUND: Telomere shortening is thought to be involved in the pathophysiology of myeloid malignancies, but telomere lengths (TL) during interphase and metaphase in hematopoietic malignancies have not been analyzed. We aimed to assess the TLs of interphase and metaphase cells of MDS and telomerase...

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Autores principales: Park, Hee Sue, Choi, Jungeun, See, Cha-Ja, Kim, Jung-Ah, Park, Si Nae, Im, Kyongok, Kim, Sung-Min, Lee, Dong Soon, Hwang, Sang Mee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society for Laboratory Medicine 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339091/
https://www.ncbi.nlm.nih.gov/pubmed/28224765
http://dx.doi.org/10.3343/alm.2017.37.3.195
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author Park, Hee Sue
Choi, Jungeun
See, Cha-Ja
Kim, Jung-Ah
Park, Si Nae
Im, Kyongok
Kim, Sung-Min
Lee, Dong Soon
Hwang, Sang Mee
author_facet Park, Hee Sue
Choi, Jungeun
See, Cha-Ja
Kim, Jung-Ah
Park, Si Nae
Im, Kyongok
Kim, Sung-Min
Lee, Dong Soon
Hwang, Sang Mee
author_sort Park, Hee Sue
collection PubMed
description BACKGROUND: Telomere shortening is thought to be involved in the pathophysiology of myeloid malignancies, but telomere lengths (TL) during interphase and metaphase in hematopoietic malignancies have not been analyzed. We aimed to assess the TLs of interphase and metaphase cells of MDS and telomerase activity (TA) and to find out prognostic significances of TL and TA. METHODS: The prognostic significance of TA by quantitative PCR and TL by quantitative fluorescence in situ hybridization (QFISH) of interphase nuclei and metaphase chromosome arms of bone marrow cells from patients with MDS were evaluated. RESULTS: MDS patients had shorter interphase TL than normal healthy donors (P<0.001). Average interphase and metaphase TL were inversely correlated (P=0.013, p arm; P=0.029, q arm), but there was no statistically significant correlation between TA and TL (P=0.258). The progression free survival was significantly shorter in patients with high TA, but the overall survival was not different according to average TA or interphase TL groups. Multivariable Cox analysis showed that old age, higher International Prognostic Scoring System (IPSS) subtypes, transformation to AML, no history of hematopoietic stem cell transplantation and short average interphase TL (<433 TL) as independent prognostic factors for poorer survival (P=0.003, 0.001, 0.005, 0.005, and 0.013, respectively). CONCLUSIONS: The lack of correlation between age and TL, TA, and TL, and the inverse relationship between TL and TA in MDS patients reflect the dysregulation of telomere status and proliferation. As a prognostic marker for leukemia progression, TA may be considered, and since interphase TL has the advantage of automated measurement by QFISH, it may be used as a prognostic marker for survival in MDS.
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spelling pubmed-53390912017-05-01 Dysregulation of Telomere Lengths and Telomerase Activity in Myelodysplastic Syndrome Park, Hee Sue Choi, Jungeun See, Cha-Ja Kim, Jung-Ah Park, Si Nae Im, Kyongok Kim, Sung-Min Lee, Dong Soon Hwang, Sang Mee Ann Lab Med Original Article BACKGROUND: Telomere shortening is thought to be involved in the pathophysiology of myeloid malignancies, but telomere lengths (TL) during interphase and metaphase in hematopoietic malignancies have not been analyzed. We aimed to assess the TLs of interphase and metaphase cells of MDS and telomerase activity (TA) and to find out prognostic significances of TL and TA. METHODS: The prognostic significance of TA by quantitative PCR and TL by quantitative fluorescence in situ hybridization (QFISH) of interphase nuclei and metaphase chromosome arms of bone marrow cells from patients with MDS were evaluated. RESULTS: MDS patients had shorter interphase TL than normal healthy donors (P<0.001). Average interphase and metaphase TL were inversely correlated (P=0.013, p arm; P=0.029, q arm), but there was no statistically significant correlation between TA and TL (P=0.258). The progression free survival was significantly shorter in patients with high TA, but the overall survival was not different according to average TA or interphase TL groups. Multivariable Cox analysis showed that old age, higher International Prognostic Scoring System (IPSS) subtypes, transformation to AML, no history of hematopoietic stem cell transplantation and short average interphase TL (<433 TL) as independent prognostic factors for poorer survival (P=0.003, 0.001, 0.005, 0.005, and 0.013, respectively). CONCLUSIONS: The lack of correlation between age and TL, TA, and TL, and the inverse relationship between TL and TA in MDS patients reflect the dysregulation of telomere status and proliferation. As a prognostic marker for leukemia progression, TA may be considered, and since interphase TL has the advantage of automated measurement by QFISH, it may be used as a prognostic marker for survival in MDS. The Korean Society for Laboratory Medicine 2017-05 2017-02-17 /pmc/articles/PMC5339091/ /pubmed/28224765 http://dx.doi.org/10.3343/alm.2017.37.3.195 Text en © The Korean Society for Laboratory Medicine http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Park, Hee Sue
Choi, Jungeun
See, Cha-Ja
Kim, Jung-Ah
Park, Si Nae
Im, Kyongok
Kim, Sung-Min
Lee, Dong Soon
Hwang, Sang Mee
Dysregulation of Telomere Lengths and Telomerase Activity in Myelodysplastic Syndrome
title Dysregulation of Telomere Lengths and Telomerase Activity in Myelodysplastic Syndrome
title_full Dysregulation of Telomere Lengths and Telomerase Activity in Myelodysplastic Syndrome
title_fullStr Dysregulation of Telomere Lengths and Telomerase Activity in Myelodysplastic Syndrome
title_full_unstemmed Dysregulation of Telomere Lengths and Telomerase Activity in Myelodysplastic Syndrome
title_short Dysregulation of Telomere Lengths and Telomerase Activity in Myelodysplastic Syndrome
title_sort dysregulation of telomere lengths and telomerase activity in myelodysplastic syndrome
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339091/
https://www.ncbi.nlm.nih.gov/pubmed/28224765
http://dx.doi.org/10.3343/alm.2017.37.3.195
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