title: Hypermethylation of SHP-1 promoter in patient with high-risk myelodysplastic syndrome and it predicts poor prognosis.
abstract: To study the role of SHP-1 methylation in the pathogenesis of myelodysplastic syndromes (MDS), we detect the methylation status of SHP-1 promoter and STAT3 phosphorylation of MDS patients by the methylation-specific PCR and Western blotting, respectively. It is found that the methylation rate of SHP-1 promoter of high-risk MDS patients (69.2%) was higher than that of the low-risk MDS patients (21.4%) (P=0.001). The expression rate of STAT3 phosphorylated protein of high-risk group was higher (66.7%), when compared with that of the low-risk group (18.2%) (P=0.0001). Correlation analysis showed that the methylation status of SHP-1 promoter is positive correlated with the expression of phosphorylated STAT3 in MDS patient (P<0.001, r=0.55). Interestingly, in high-risk group, the Kaplan-Meier analysis showed that the 3-year overall survival rate of high-risk MDS patients with SHP-1 methylation was lower than that of patient without SHP-1 methylation (25% vs. 61%) (P=0.033). In summary, it is indicated that the SHP-1 methylation plays important role in the pathogenesis of MDS via activating the JAK/STAT pathway probably and the methylation of SHP-1 promoter is a useful prognostic factor for high-risk MDS patient, with the characteristic of higher methylation lower survival rate.
authors.affiliation: Department of Hematology, Tianjin Cancer Hospital and Institute, Tianjin Medical University, Tianjin, 300060, People's Republic of China. zhangzhurensci@yahoo.cn
authors.forename: Yizhuo
authors.initials: Y
authors.lastname: Zhang
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhao
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhao
authors.forename: Xiaoxiong
authors.initials: X
authors.lastname: Wu
authors.forename: Weipeng
authors.initials: W
authors.lastname: Zhao
authors.forename: Yafei
authors.initials: Y
authors.lastname: Wang
authors.forename: Bing
authors.initials: B
authors.lastname: Xia
authors.forename: Wanming
authors.initials: W
authors.lastname: Da
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000401:mortality; D010766:Phosphorylation; D011379:Prognosis; D011401:Promoter Regions, Genetic; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics*; D012306:Risk; D050796:STAT3 Transcription Factor / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: D050796:STAT3 Transcription Factor; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6