Downregulation of p21 in myelodysplastic syndrome is associated with p73 promoter hypermethylation and indicates poor prognosis.
OBJECTIVE
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.
Dept of Hematology, Shanghai Sixth People's Hospital affiliated to Shanghai Jiaotong University, 200233 Shanghai, China; changchunkang7010@aliyun.com.
Youshan
Y
Zhao
Juan
J
Guo
Xi
X
Zhang
Zheng
Z
Zhang
Shucheng
S
Gu
Chengmin
C
Fei
Xiao
X
Li
Chunkang
C
Chang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
D014408:Biomarkers, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
Cell cycle; MDS; p21; p73