巯嘌呤和甲氨蝶呤治疗急性淋巴性白血病的基因调控差异共表达分析  

Differential Analysis of Gene Regulation in Human Leukemia Cells in Response to Methotrexate and Mercaptopurine

作　　者：杨爽[1,2] 杨竞[2,3] 李贞[2,4] 吴素娟[2,3] 付鹏[2,3] 李亦学[1,2,5,3] 孙红[2,5] 

机构地区：[1]同济大学生命科学与技术学院,上海200092 [2]上海生物信息技术研究中心,上海200235 [3]华东理工大学生物工程学院,上海200237 [4]上海交通大学生命科学与技术学院,上海200240 [5]中国科学院上海生命科学院系统生物学重点实验室,上海200031

出　　处：《生物物理学报》2014年第2期157-164,共8页Acta Biophysica Sinica

基　　金：国家自然科学基金项目(31371343);"973"计划项目(2010CB529202;2011CB510102)~~

摘　　要：复杂疾病往往由于错综复杂的遗传和环境因素相互作用而引起,并严重危害着人类健康。因此,对相关药物疗效的研究,特别是对其作用分子机理的阐释就显得尤为重要。常用的寻找表达量有差异的基因的方法不能准确地反映出药物影响下基因间的相互作用关系。作者利用差异共表达分析方法,研究了巯嘌呤、甲氨蝶呤及联合用药在治疗急性淋巴性白血病中的潜在分子机理。分析了四种给药方式给药前后的基因差异共表达关系及差异共表达调控基因的作用特征。系统解析了联合用药和单独用药治疗急性淋巴性白血病在分子机理上的异同。Complex diseases are caused by a combination of genetic and environmental factors, and severely impair humanity＇s health. So, it is especially important to uncover the molecular mechanism underlying the drug effects on complex diseases. Traditional ＇differential expression analysis＇ looks at absolute changes in gene expression levels, and fails to explore the gene interconnection in response to drug treatments. Using ＇differential coexpression analysis＇ method, the authors analyzed the molecular regulatory mechanism in acute lymphoblastic leukemia cells in response to the four types of treatments, i.e. methotrexate and mercaptopurine given alone or in combination. The co-expression and regulatory relationships between genes were investigated before and after the treatments. The study illuminates the regulatory differences in leukemia cellular response to drug combinations versus single agents in a systems perspective.

关 键 词：联合用药 分子机理 差异共表达 转录调控 

分 类 号：R9[医药卫生—药学] Q7[生物学—分子生物学]