Journal
MEDICAL ONCOLOGY
Volume 29, Issue 4, Pages 2359-2363Publisher
HUMANA PRESS INC
DOI: 10.1007/s12032-012-0163-6
Keywords
SHP-1; Methylation; STAT3; Myelodysplastic syndrome
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Funding
- National Natural Science Foundation of China [30672208, 81100337]
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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.
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