| Title: |
Hypermethylation of CpG sites at the promoter region is associated with deregulation of mitochondrial ATPsyn-β and chemoresistance in acute myeloid leukemia. |
| Authors: |
Jingke Yang, Xiang Xiao, Ruijuan Li, Zijian Li, Mingyang Deng, Guangsen Zhang |
| Source: |
Cancer Biomarkers; 2016, Vol. 16 Issue 1, p81-88, 8p |
| Subject Terms: |
MITOCHONDRIA, ACUTE myeloid leukemia, DNA methylation, METHYLATION, DOXORUBICIN |
| Abstract: |
BACKGROUND: Aberrant DNA methylation status of some genes has been shown to be involved in chemoresistance of acute myeloid leukemia (AML).We have recently found that down-regulation of the β subunit of mitochondrial ATP synthase (ATPsyn- β) leads to adriamycin resistance in acute and chronic myeloid leukemia cells, and hypermethylation of the ATPsyn-β gene promoter is associated with chemoresistance in chronic myeloid leukemia. OBJECTIVE: To further investigate the relationship between methylation of ATPsyn-β gene, mRNA expression as well as chemoresistance in AML. METHODS: Quantitative RT-PCR and methylation specific PCR were performed to assess mRNA expression and methylation status of ATPsyn-β gene on primary bone marrow nuclear cells (BMMCs), and cell proliferation assay was used to determine the sensitivity of BMMCs to adriamycin. RESULTS: Hypermethylation status of ATPsyn-β gene promoter existed in those relapsed/refractory AML patients, and this hypermethylation of the gene was associated with a suppressed mRNA expression levels. Four patients at diagnosis and relapse underwent gene methylation status shift from hypermethylation to hypomethylation, which was accompanied by reduced mRNA expression of the gene. 5-azacitidine(5-Aza)- a demethylating agent, could restore ATPsyn-β mRNA expression and increase the adriamycin sensitivity of primary leukemic cells from seven relapsed/ refractory AML patients. CONCLUSIONS: Hypermethylation of ATPsyn-β gene promoter is associated with a down-regulated mRNA expression and chemoresistance in AML patients. [ABSTRACT FROM AUTHOR] |
|
Copyright of Cancer Biomarkers is the property of IOS Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Complementary Index |
