Hypermethylation of SHP-1 promoter in patient with high-risk myelodysplastic syndrome and it predicts poor prognosis.

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.