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

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 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.