NDLI: Methylation of the p73 gene in patients with myelodysplastic syndromes: correlations with apoptosis and prognosis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zhao, Youshan Fei, Chengming Zhang, Xi Zhang, Yao Guo, Juan Gu, Shucheng Li, Xiao Chang, Chunkang
Description	Country affiliation: China Author Affiliation: Zhao Y ( Department of Hematology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, 200233, Shanghai, China.)
Abstract	The identification of epigenetically inactivated tumor suppressor genes may shed additional light on the pathogenesis of myelodysplastic syndromes (MDS) and lead to the identification of potential therapeutic targets for demethylating agents. In this study, the methylation status of the p73 gene promoter was analyzed by methylation-specific PCR (MS-PCR) in bone marrow (BM) samples from 126 adult patients with de novo MDS. The results of the MS-PCR were confirmed by bisulfite sequencing. In addition, we analyzed p73 expression using real-time PCR. The apoptosis of BM cells was examined by flow cytometry. The methylation of the p73 gene was observed in 36.5 % of cases. There were strong correlations between p73 methylation and the marrow blast levels (p = 0.037) and the WHO classification (p = 0.016). The frequency of p73 methylation was significantly correlated with the International Prognostic Scoring System subgroup ( r = 0.904, p < 0.001). Moreover, a decrease in the transcription of p73 was accompanied by methylation (p = 0.032). Although the level of apoptosis in the BM samples of the methylated group was not significantly lower than that in the unmethylated group (p = 0.094), decitabine treatment restored p73 expression and increased the level of cytarabine (ara-C)-induced apoptosis in vitro. The median survival time of patients with p73 methylation was shorter than that for patients without p73 methylation (15 vs. > 33 months, respectively, p = 0.002). A multivariate analysis also indicated that the p73 methylation status was the independent factor that impacted overall survival. In conclusion, p73 methylation is common in patients with MDS and is associated with poor prognosis. Our results provide further evidence for the involvement of epigenetic dysregulation in the pathogenesis of MDS.
File Format	HTM / HTML
ISSN	10104283
Issue Number	1
Volume Number	34
e-ISSN	14230380
Journal	Tumor Biology
Language	English
Publisher	Springer
Publisher Date	2013-02-01
Publisher Place	Netherlands
Access Restriction	Subscribed
Subject Keyword	Discipline Medicine__semicolon__oncology Apoptosis Bone Marrow Cells Pathology Dna Methylation Dna-binding Proteins Genetics Myelodysplastic-myeloproliferative Diseases Nuclear Proteins Tumor Suppressor Proteins Adult Aged Azacitidine Analogs & Derivatives Pharmacology Cells, Cultured Cytarabine Female Humans Male Middle Aged Mortality Prognosis Promoter Regions, Genetic Survival Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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