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- Title
GPX3 methylation in bone marrow predicts adverse prognosis and leukemia transformation in myelodysplastic syndrome.
- Authors
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
- Abstract
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.
- Subjects
GLUTATHIONE peroxidase; BONE marrow; LEUKEMIA; MYELODYSPLASTIC syndromes; DNA methylation; POLYMERASE chain reaction
- Publication
Cancer Medicine, 2017, Vol 6, Issue 1, p267
- ISSN
2045-7634
- Publication type
Article
- DOI
10.1002/cam4.984