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Hypermethylation of CpG sites at the promoter region is associated with deregulation of mitochondrial ATPsyn-β and chemoresistance in acute myeloid leukemia.
- Source :
-
Cancer biomarkers : section A of Disease markers [Cancer Biomark] 2016; Vol. 16 (1), pp. 81-8. - Publication Year :
- 2016
-
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.<br />Objective: To further investigate the relationship between methylation of ATPsyn-β gene, mRNA expression as well as chemoresistance in AML.<br />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.<br />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.<br />Conclusions: Hypermethylation of ATPsyn-β gene promoter is associated with a down-regulated mRNA expression and chemoresistance in AML patients.
- Subjects :
- Adult
Aged
Azacitidine pharmacology
Case-Control Studies
Female
Gene Expression
Humans
Leukemia, Myeloid, Acute diagnosis
Leukemia, Myeloid, Acute drug therapy
Male
Middle Aged
Recurrence
Remission Induction
Young Adult
CpG Islands
DNA Methylation
Drug Resistance, Neoplasm genetics
Leukemia, Myeloid, Acute genetics
Mitochondrial Proton-Translocating ATPases genetics
Promoter Regions, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 1875-8592
- Volume :
- 16
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cancer biomarkers : section A of Disease markers
- Publication Type :
- Academic Journal
- Accession number :
- 26835708
- Full Text :
- https://doi.org/10.3233/CBM-150543