Shucheng Gu, Chunkang Chang, Youshan Zhao, Juan Guo, Chengming Fei, Xi Zhang, Chao Xiao, Xiao Li
Department of Hematology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University , Shanghai , China.
Cancer Invest. 2015 Apr;33(4):98-106. doi: 10.3109/07357907.2014.1001895. Epub 2015 Feb 20.
In order to research how does hypomethylating agents ameliorate iron metabolism in myelodysplastic syndrome (MDS), we performed methylation-specific, polymerase chain reaction (MSP), bisulfate genomic sequencing polymerase chain reaction (BSP), quantitative real-time PCR and western blot of hemojuvelin (HJV) and ELISA assay for hepcidin before and after demethylating therapy (decitabine) to determine whether the change of HJV methylation status would have an influence on hepcidin expression. Eleven of 22 MDS patients achieved CR or PR according to IWG criteria (50%). HJV mRNA was induced in decitabine responders (p = .006 comparing pre/post decitabine treatment) but not in non-responders (p = .121). Similarly, hepcidin serum expression increased from 320.77 ± 34.8 μg/L to 366.77 ± 21.90 μg/L (p = .012) in responders but did not significantly change in non-responders (p = .058), while no difference of adjusted serum ferritin (ASF) was found. In conclusion, hypermethylation of HJV promoter region could silence the gene expression and demethylating therapy might ameliorate iron-overload through HJV demethylation.
为了研究低甲基化剂如何改善骨髓增生异常综合征（MDS）中的铁代谢，我们在去甲基化治疗（地西他滨）前后进行了甲基化特异性聚合酶链反应（MSP）、亚硫酸氢盐基因组测序聚合酶链反应（BSP）、铁调素（HJV）的定量实时PCR和蛋白质免疫印迹以及铁调素的酶联免疫吸附测定（ELISA），以确定HJV甲基化状态的变化是否会影响铁调素的表达。根据国际工作组（IWG）标准，22例MDS患者中有11例达到完全缓解（CR）或部分缓解（PR）（50%）。地西他滨治疗有反应者的HJV mRNA水平升高（地西他滨治疗前后比较，p = 0.006），而无反应者则未升高（p = 0.121）。同样，有反应者的血清铁调素表达从320.77±34.8μg/L升高至366.77±21.90μg/L（p = 0.012），无反应者则无显著变化（p = 0.058），而校正后的血清铁蛋白（ASF）无差异。总之，HJV启动子区域的高甲基化可能使基因表达沉默，而去甲基化治疗可能通过HJV去甲基化改善铁过载。
