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GPX3 methylation in bone marrow predicts adverse prognosis and leukemia transformation in myelodysplastic syndrome

Epigenetic inactivation of GPX3 has been identified in various cancers including leukemia. Moreover, aberrant DNA methylation was also found as a dominant mechanism of disease progression in myelodysplastic syndrome (MDS). This study intended to explore GPX3 promoter methylation and its clinical rel...

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Autores principales: Zhou, Jing‐Dong, Lin, Jiang, Zhang, Ting‐Juan, Ma, Ji‐Chun, Yang, Lei, Wen, Xiang‐Mei, Guo, Hong, Yang, Jing, Deng, Zhao‐Qun, Qian, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5269561/
https://www.ncbi.nlm.nih.gov/pubmed/27891827
http://dx.doi.org/10.1002/cam4.984
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author Zhou, Jing‐Dong
Lin, Jiang
Zhang, Ting‐Juan
Ma, Ji‐Chun
Yang, Lei
Wen, Xiang‐Mei
Guo, Hong
Yang, Jing
Deng, Zhao‐Qun
Qian, Jun
author_facet Zhou, Jing‐Dong
Lin, Jiang
Zhang, Ting‐Juan
Ma, Ji‐Chun
Yang, Lei
Wen, Xiang‐Mei
Guo, Hong
Yang, Jing
Deng, Zhao‐Qun
Qian, Jun
author_sort Zhou, Jing‐Dong
collection PubMed
description Epigenetic inactivation of GPX3 has been identified in various cancers including leukemia. Moreover, aberrant DNA methylation was also found as a dominant mechanism of disease progression in myelodysplastic syndrome (MDS). This study intended to explore GPX3 promoter methylation and its clinical relevance in 110 patients with MDS. GPX3 methylation was examined by real‐time quantitative methylation‐specific PCR (RQ‐MSP) and bisulfite sequencing PCR (BSP). GPX3 methylation was identified in 15% (17/110) MDS patients, and significantly higher than controls, and lower than acute myeloid leukemia (AML) patients (P = 0.024 and 0.041). GPX3 methylated patients had older age and higher frequency of DNMT3A mutation (P = 0.015 and 0.066). Cases with GPX3 methylation showed significantly shorter overall survival (OS) time than those with GPX3 unmethylation analyzed with Kaplan–Meier analysis (P = 0.012). Moreover, Cox regression analysis revealed that GPX3 methylation might act as an independent prognostic indicator in MDS (HR = 1.847, P = 0.072). GPX3 methylation density was significantly increased during the progression from MDS to secondary acute myeloid leukemia (sAML) in three follow‐up paired patients. Our study concludes that GPX3 methylation in bone marrow is associated with adverse prognosis and leukemia transformation in MDS.
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spelling pubmed-52695612017-02-01 GPX3 methylation in bone marrow predicts adverse prognosis and leukemia transformation in myelodysplastic syndrome Zhou, Jing‐Dong Lin, Jiang Zhang, Ting‐Juan Ma, Ji‐Chun Yang, Lei Wen, Xiang‐Mei Guo, Hong Yang, Jing Deng, Zhao‐Qun Qian, Jun Cancer Med Cancer Biology Epigenetic inactivation of GPX3 has been identified in various cancers including leukemia. Moreover, aberrant DNA methylation was also found as a dominant mechanism of disease progression in myelodysplastic syndrome (MDS). This study intended to explore GPX3 promoter methylation and its clinical relevance in 110 patients with MDS. GPX3 methylation was examined by real‐time quantitative methylation‐specific PCR (RQ‐MSP) and bisulfite sequencing PCR (BSP). GPX3 methylation was identified in 15% (17/110) MDS patients, and significantly higher than controls, and lower than acute myeloid leukemia (AML) patients (P = 0.024 and 0.041). GPX3 methylated patients had older age and higher frequency of DNMT3A mutation (P = 0.015 and 0.066). Cases with GPX3 methylation showed significantly shorter overall survival (OS) time than those with GPX3 unmethylation analyzed with Kaplan–Meier analysis (P = 0.012). Moreover, Cox regression analysis revealed that GPX3 methylation might act as an independent prognostic indicator in MDS (HR = 1.847, P = 0.072). GPX3 methylation density was significantly increased during the progression from MDS to secondary acute myeloid leukemia (sAML) in three follow‐up paired patients. Our study concludes that GPX3 methylation in bone marrow is associated with adverse prognosis and leukemia transformation in MDS. John Wiley and Sons Inc. 2016-11-28 /pmc/articles/PMC5269561/ /pubmed/27891827 http://dx.doi.org/10.1002/cam4.984 Text en © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cancer Biology
Zhou, Jing‐Dong
Lin, Jiang
Zhang, Ting‐Juan
Ma, Ji‐Chun
Yang, Lei
Wen, Xiang‐Mei
Guo, Hong
Yang, Jing
Deng, Zhao‐Qun
Qian, Jun
GPX3 methylation in bone marrow predicts adverse prognosis and leukemia transformation in myelodysplastic syndrome
title GPX3 methylation in bone marrow predicts adverse prognosis and leukemia transformation in myelodysplastic syndrome
title_full GPX3 methylation in bone marrow predicts adverse prognosis and leukemia transformation in myelodysplastic syndrome
title_fullStr GPX3 methylation in bone marrow predicts adverse prognosis and leukemia transformation in myelodysplastic syndrome
title_full_unstemmed GPX3 methylation in bone marrow predicts adverse prognosis and leukemia transformation in myelodysplastic syndrome
title_short GPX3 methylation in bone marrow predicts adverse prognosis and leukemia transformation in myelodysplastic syndrome
title_sort gpx3 methylation in bone marrow predicts adverse prognosis and leukemia transformation in myelodysplastic syndrome
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5269561/
https://www.ncbi.nlm.nih.gov/pubmed/27891827
http://dx.doi.org/10.1002/cam4.984
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