National Hematological Medical Center of Traditional Chinese Medicine, Department of Hematology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
Evid Based Complement Alternat Med. 2012;2012:969476. doi: 10.1155/2012/969476. Epub 2012 Oct 16.
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.
我们之前已经表明,含砷中药配方青黄散(含四硫化四砷,As(4)S(4))在骨髓增生异常综合征(MDS)的治疗中是有效的;然而,其潜在机制尚不清楚。在这项研究中,我们使用标准细胞遗传学分析(G 带)和全基因组甲基化方法(ChIP-on-chip 检测),旨在确定含砷中药配方对初诊 MDS 患者核型状态和基因组甲基化水平的影响。还研究了 MDS 中异常 DNA 甲基化与染色体异常之间的相关性。我们发现,在核型正常的 MDS 患者中,异常 DNA 甲基化的基因数量最多,其次是 8 三体核型,而除 8 三体以外的细胞遗传学异常患者中基因数量相对较低。含砷中药配方治疗对核型状态没有影响,但导致全基因组去甲基化。我们的研究揭示了含砷中药配方在 MDS 治疗中的 DNA 去甲基化活性。