Dataset Information

Karyotype and DNA-Methylation Responses in Myelodysplastic Syndromes following Treatment with Traditional Chinese Formula Containing Arsenic.

ABSTRACT: We have previously shown that arsenic-containing Chinese herbal formula, Qing-Huang powder capsule (containing tetraarsenic tetrasulfide, As(4)S(4)), is effective in the treatment of myelodysplastic syndrome (MDS); yet the underlined mechanisms remain unclear. In this study, using standard cytogenetic analysis (G-banded) and global DNA methylation method (ChIP-on-chip assays), we aimed to determine the effect of arsenic-containing Chinese herbal formula on karyotype status and the genomic methylation level in primarily diagnosed MDS patients. Correlation of aberrant DNA methylation and chromosome aberrations in MDS was also investigated. We found that the number of genes with aberrant DNA methylation was highest in MDS patients with normal karyotype, followed by trisomy 8 karyotype, and relatively low in patients with cytogenetic abnormalities other than trisomy 8. Treatment with arsenic-containing Chinese herbal formula had no effects on karyotype status, but resulted in a significant genome-wide demethylation. Our research uncovered a DNA demethylating activity of arsenic-containing Chinese herbal formula in the treatment of MDS.

SUBMITTER: Shuzhen S

PROVIDER: S-EPMC3480675 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Karyotype and DNA-Methylation Responses in Myelodysplastic Syndromes following Treatment with Traditional Chinese Formula Containing Arsenic.

Shuzhen Sun S Rou Ma M Xiaomei Hu H Xiao-Hong Yang Y Yong-Gang Xu X Hongzhi Wang W Xiu-Peng Yang Y

Evidence-based complementary and alternative medicine : eCAM 20121016

We have previously shown that arsenic-containing Chinese herbal formula, Qing-Huang powder capsule (containing tetraarsenic tetrasulfide, As(4)S(4)), is effective in the treatment of myelodysplastic syndrome (MDS); yet the underlined mechanisms remain unclear. In this study, using standard cytogenetic analysis (G-banded) and global DNA methylation method (ChIP-on-chip assays), we aimed to determine the effect of arsenic-containing Chinese herbal formula on karyotype status and the genomic methyl ...[more]

PMID: 23118798

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Project description:Genome-wide expression and methylation profiling identifies novel targets with aberrant hypermethylation and reduced expression in low-risk myelodysplastic syndromes (MDSs). Gene expression profiling signatures may be used to classify the subtypes of Myelodysplastic syndrome (MDS) patients. However, there are few reports on the global methylation status in MDS. The integration of genome-wide epigenetic regulatory marks with gene expression levels would provide additional information regarding the biological differences between MDS and healthy controls. Gene expression and methylation status were measured using high-density microarrays. A total of 552 differentially methylated CpG loci were identified as being present in low-risk MDS; hypermethylated genes were more frequent than hypomethylated genes. In addition, mRNA expression profiling identified 1005 genes that significantly differed between low-risk MDS and the control group. Integrative analysis of the epigenetic and expression profiles revealed that 66.7% of the hypermethylated genes were underexpressed in low-risk MDS cases. Gene network analysis revealed molecular mechanisms associated with the low-risk MDS group, including altered apoptosis pathways. The two key apoptotic genes BCL2 and ETS1 were identified as silenced genes. In addition, the immune response and micro RNA biogenesis were affected by the hypermethylation and underexpression of IL27RA and DICER1. Our integrative analysis revealed that aberrant epigenetic regulation is a hallmark of low-risk MDS patients and could have a central role in these diseases. Low-risk MDS patients and age-matched controls without haematological malignancies were included in the study. Mononuclear cells were isolated from bone marrow samples of low-risk MDS patients and controls by density gradient (Ficoll). A cohort of 18 patients with low-risk MDS and seven controls were included in a simultaneous integrative study of methylation (using Methylated CpG Island Amplification and Microarrays, MCAM) and expression (using Affymetrix microarrays HG-U133 Plus 2), while the whole series was used as a control group of expression data.

Dataset Information

Karyotype and DNA-Methylation Responses in Myelodysplastic Syndromes following Treatment with Traditional Chinese Formula Containing Arsenic.

Publications

Karyotype and DNA-Methylation Responses in Myelodysplastic Syndromes following Treatment with Traditional Chinese Formula Containing Arsenic.

Similar Datasets

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