急性髓系白血病中异柠檬酸脱氢酶1基因突变的生物信息学分析

Bioinformatics Analysis for Isocitrate Dehydrogenase 1 Mutation in Acute Myeloid Leukemia

目的从分子水平揭示合并异柠檬酸脱氢酶1(IDH1)基因突变的正常核型急性髓系白血病(CN-AML)患者的发病机制,为临床诊疗提供新工具。方法在GEO中检索IDH1突变的AML芯片数据,使用BRB-Array Tools、GSEA、MILANO、GAD、GATHER等生物信息学工具进行统合分析。结果经过2组样本数据的统合分析,发现12个差异表达基因,主要集中在细胞粘附、免疫防御反应等生物学过程。与参与凋亡、Toll-like、Jak-Stat等信号通路有关。GSEA分析表明IDH1相关基因分别涉及到脂质代谢、髓系细胞分化和缺氧调节等方面。结论利用生物信息学的方法能提取基因芯片有效信息,为进一步深入研究IDH1在CN-AML的发病机制中的作用开辟新思路。

Objective To understand the molecular pathogenesis of isocitrate dehydrogenase 1（IDH1）mutation in the subgroup of cytogenetically normal acute myeloid leukemia（CN-AML）,and provide novel means for clinical diagnosis and treatment of AML.Methods Gene expression profiles were obtained from GEO database,and a set of bioinformatics tools,such as BRB-Array Tools,GSEA,MILANO,GAD,GATHER were used to accomplish the data-mining.Results After combined the results of two independent sample sets,12 differentially expressed genes were identified,which were involved in cell adhesion,immunity,etc.IDH1 related genes played essential roles in such important signal pathway Toll-like,Jak-Stat.GSEA analysis results suggested that IDH1-related genes might mainly affect the biological progress in lipid metabolism,myeloid cell differentiation and hypoxia regulation.Conclusion Bioinformatics analysis can effectively process the gene chip data.The pathogenesis of IDH1 mutation involves abnormal expression of multiple genes,and these data may benefit further investigations of the pathogenesis of CN-AML with IDH1 mutation.