Lu Xue-Chun, Yang Bo, Zhu Hong-Li, Fan Hui, Li Su-Xia, Liu Yang, Yao Shan-Qian
Department of Geriatric Hematology, Chinese PLA General Hospital, Beijing 100853, China.
Zhonghua Yi Xue Za Zhi. 2009 Jul 14;89(26):1834-7.
To apply bioinformatics analysis to study the potential mechanism of amifostine for the treatment of myelodysplastic syndrome (MDS) and optimize amifostine combination regimen to further improve the efficacy and prognosis of MDS.
Bioinformatics analysis: Internet-based human gene expression open database was used to predict the genomic profiling by regulation of amifostine and gene expression of MDS. And then possible target genes of amifostine were screened to predict the feasibility of amifostine combination regimen. Finally, similar analysis of gene expression profiling was conducted to forecast the potential therapeutic drugs for MDS. Clinical investigation: eighteen patients with MDS, non-responding to traditional drugs, were enrolled. According to the latest WHO classification, the patients were divided into 7 patients of refractory anemia (RA), 2 patients of refractory anemia with ring sideroblast (RARS) and 9 patients of refractory cytopenia with multilineage dysplasia (RCMD). Distributions of age was 19-91 years old (mean: 79). There were 17 males and 1 female. The regimen of amifostine plus recombinant human erythropoietin (rhEPO) was used to treat the MDS patients. Administration formula was as follows: the intravenous drip of amifostine at a dosage of 0.4 gram per day was given 5 days weekly for 4 consecutive weeks; the subcutaneous injection of rhEPO at a dosage of 6 000 IU was given 3 times weekly. Therapeutic effect was evaluated 2 weeks post-therapy.
Approximately 2.6 percent of human gene involved in apoptosis, cell cycle and differentiation was regulated by amifostine. Especially, upregulation of ELK1 expression, which belongs to downstream functional gene of EPO pathway, and downregulation of Cyclin D1 expression were successfully predicted. Based on the potential therapeutic mechanism amifostine for MDS, amifostine plus EPO had dual effects on MDS, i. e. promotion of hematopoiesis and inhibition of tumor cell proliferation. Clinical investigation showed that the response rates of hemoglobin, neutrophil and platelet were 83.3%, 66.7% and 55.6% respectively. The results suggested that the regimen of amifostine plus EPO had better therapeutic effects than a single agent.
The study successfully used bioinformatics analysis to screen target genes regulated by amifostine and optimize amifostine combination therapeutic regimen for MDS. Bioinformatics method is a convenient, economical and effective supplementary approach for studying the pathogenesis and therapeutics of MDS.
应用生物信息学分析研究氨磷汀治疗骨髓增生异常综合征（MDS）的潜在机制，并优化氨磷汀联合治疗方案，以进一步提高MDS的疗效和预后。
生物信息学分析：利用基于互联网的人类基因表达开放数据库，通过氨磷汀调控及MDS基因表达预测基因组图谱。然后筛选氨磷汀可能的靶基因，预测氨磷汀联合治疗方案的可行性。最后进行基因表达谱的相似性分析，预测MDS的潜在治疗药物。临床研究：纳入18例对传统药物无反应的MDS患者。根据世界卫生组织最新分类，患者分为难治性贫血（RA）7例、环形铁粒幼细胞难治性贫血（RARS）2例、多系发育异常难治性血细胞减少症（RCMD）9例。年龄分布为19 - 91岁（平均79岁）。男性17例，女性1例。采用氨磷汀加重组人促红细胞生成素（rhEPO）方案治疗MDS患者。给药方案如下：氨磷汀每日0.4克静脉滴注，每周5天，连续4周；rhEPO 6000 IU皮下注射，每周3次。治疗2周后评估疗效。
约2.6%参与凋亡、细胞周期和分化的人类基因受氨磷汀调控。特别是，成功预测了属于EPO途径下游功能基因的ELK1表达上调和细胞周期蛋白D1表达下调。基于氨磷汀对MDS的潜在治疗机制，氨磷汀加EPO对MDS有双重作用，即促进造血和抑制肿瘤细胞增殖。临床研究表明，血红蛋白、中性粒细胞和血小板的反应率分别为83.3%、66.7%和55.6%。结果提示氨磷汀加EPO方案的治疗效果优于单一药物。
本研究成功利用生物信息学分析筛选出受氨磷汀调控的靶基因，并优化了MDS的氨磷汀联合治疗方案。生物信息学方法是研究MDS发病机制和治疗方法的一种便捷、经济有效的辅助手段。
