Abstract
BackgroundAccumulating evidence supports a role of DNA methylation in the pathogenesis of leukemia. The aim of our study was to evaluate the potential genes with aberrant DNA methylation in the prediction of leukemia risk by a comprehensive meta-analysis of the published data.MethodsA series of meta-analyses were done among the eligible studies that were harvested after a careful filtration of the searching results from PubMed literature database. Mantel-Haenszel odds ratios and 95% confidence intervals were computed for each methylation event assuming the appropriate model.ResultsA total of 535 publications were initially retrieved from PubMed literature database. After a three-step filtration, we harvested 41 case-control articles that studied the role of gene methylation in the prediction of leukemia risk. Among the involving 30 genes, 20 genes were shown to be aberrantly methylated in the leukemia patients. A further subgroup meta-analysis by subtype of leukemia showed that CDKN2A, CDKN2B, ID4 genes were significantly hypermethylated in acute myeloid leukemia.ConclusionsOur meta-analyses identified strong associations between a number of genes with aberrant DNA methylation and leukemia. Further studies should be required to confirm the results in the future.
Highlights
Leukemia is a common malignant disease of hematopoietic system, caused by unbalanced hematopoietic cells proliferation and death [1]
Our results showed a significant heterogeneity among the 5 case-control studies (I2 = 56%), and revealed that hypermethylation of CDKN2B gene was associated with the increased risk of leukemia (P = 0.001, OR = 9.67, 95% CI = 2.48–37.75)
We found that DNA methylation of CDKN2A gene was significantly associated with acute myeloid leukemia (AML), but not with chronic myeloid leukemia (CML) or chronic lymphocytic leukemia (CLL)
Summary
Leukemia is a common malignant disease of hematopoietic system, caused by unbalanced hematopoietic cells proliferation and death [1]. Tremendous efforts have been made in the identification of susceptible factors of leukemia [2,3], the pathogenesis of leukemia is not fully clarified [4]. Environmental factors, such as high benzene exposure, radiation, electrical work, are shown to be associated with the development of leukemia [5,6]. Accumulating evidence supports a role of DNA methylation in the pathogenesis of leukemia. The aim of our study was to evaluate the potential genes with aberrant DNA methylation in the prediction of leukemia risk by a comprehensive meta-analysis of the published data
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