Downregulation of p21 in Myelodysplastic Syndrome Is Associated With p73 Promoter Hypermethylation and Indicates Poor Prognosis

Objectives: p21 Can both promote and inhibit tumorigenic processes. We explored the role of p21 in myelodysplastic syndrome (MDS). Methods: In this study, we analyzed p21 expression and p73 methylation in 88 patients with de novo MDS. Results: We found decreased expression of the p21 gene in higher-risk MDS compared with lower-risk groups or healthy controls (P < .05). Patients with p73 methylation had lower p21 than those in the unmethylated group (P < .001). Moreover, there was a significantly positive correlation between p73 and p21 expression in MDS (r = 0.436, P < .001). In vitro assays further confirm the role of p73 methylation in p21 expression. Compared with patients with normal expression levels of p21, patients with lower p21 expression levels experienced much higher rates of transformation to acute myeloid leukemia and lower overall survival both in univariate as well as multivariate analyses. Conclusions: Our results suggest p21 expression may serve as a new biomarker to predict clinical outcome in patients with MDS. (C) American Society for Clinical Pathology