Methylation of CHD5 Gene Promoter Regulates p19Arf/p53/p21Cip1 Pathway to Facilitate Pathogenesis of Acute Myeloid Leukemia

Abstract

To investigate the methylation status of CHD5 gene promoter in bone marrow from acute myeloid leukemia (AML) patients, and the underlying mechanism for initiating the pathogenesis of AML via p19Arf/p53/p21Cip1 pathway. Methylation status of the CHD5 gene promoter was detected by using methylation-specific polymerase chain reaction (MSPCR) in bone marrow from AML patients, and the iron-deficiency anemia (IDA) samples were served as control. The expression of CHD5, p19Arf, p53 and p21Cip1 was determined by real-time quantitative reverse transcriptase PCR and Western blot. The methylation of CHD5 gene in bone marrow from AML patients increased significantly (39.06%) as compared with control group (6.67%). The methylation of CHD5 gene significantly correlated with chromosome karyotype differentiation (P＜0.01), but did not correlate with the patient's sex, age and clinical classification (P＞0.05). The mRNA expression of CHD5 gene in AML decreased, compared with control group, the mRNA and protein expression of p19Arf, p53 and p21Cip1 in AML with CHD5 methylation promoter decreased. The hypermeltylation of CHD5 gene promoter in AML patients can lead to decrease of CHD5, p19Arf, p53 and p21Cip1 expression levels which may reduce the inhibitory effect on proliferation of leukemia cells through the regulation of p19Arf, p53 and p21Cip1 pathway, thus promotes the occurence of AML.