Methylation of CHD5 Gene Promoter Regulates p19/p53/p21 Pathway to Facilitate Pathogenesis of Acute Myeloid Leukemia.
10.19746/j.cnki.issn.1009-2137.2019.04.002
- Author:
Ming-Cai WU
1
;
Ming JIANG
2
;
Ting DONG
3
;
Jun LV
1
;
Ji-Yong FANG
4
;
Lei XU
1
;
Zhong-Ling WEI
5
;
Yao ZHANG
6
Author Information
1. Department of Biochemistry of Wannan Medical College, Wuhu 241002, Anhui Province, China,Anhui Province Key Laboratory of Active Biological Macromolecules, Wuhu 241002, Anhui Province, China.
2. Wuhu Second Sanatorium for Retired Cadres, Anhui Military Area, Wuhu 241001, Anhui Province, China.
3. Encephalopathy Center, The First Affiliated Hospital of the University of Traditional Chinese Medicine in Anhui, Hefei 230031, Anhui Province，China.
4. Department of Biochemistry of Wannan Medical College, Wuhu 241002, Anhui Province, China.
5. Department of Hematology, Yijishan Hospital, Wannan Medical College, Wuhu 241001, Anhui Province, China.
6. Department of Biochemistry of Wannan Medical College, Wuhu 241002, Anhui Province, China,Anhui Province Key Laboratory of Active Biological Macromolecules, Wuhu 241002, Anhui Province, China,E-mail: zhangyao@ahedu.gov.cn.
- Publication Type:Journal Article
- MeSH:
Cyclin-Dependent Kinase Inhibitor p16;
Cyclin-Dependent Kinase Inhibitor p21;
DNA Helicases;
DNA Methylation;
Humans;
Leukemia, Myeloid, Acute;
Nerve Tissue Proteins;
Promoter Regions, Genetic;
Tumor Suppressor Protein p53
- From:
Journal of Experimental Hematology
2019;27(4):1001-1007
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE: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 p19/p53/p21 pathway.
METHODS: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, p19, p53 and p21 was determined by real-time quantitative reverse transcriptase PCR and Western blot.
RESULTS: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 p19, p53 and p21 in AML with CHD5 methylation promoter decreased.
CONCLUSION:The hypermeltylation of CHD5 gene promoter in AML patients can lead to decrease of CHD5, p19, p53 and p21 expression levels which may reduce the inhibitory effect on proliferation of leukemia cells through the regulation of p19, p53 and p21 pathway, thus promotes the occurence of AML.
