Relationship of differential gene expression profiles in CD34+ myelodysplastic syndrome marrow cells to disease subtype and progression.
Relationship of differential gene expression profiles in CD34+ myelodysplastic syndrome marrow cells to disease subtype and progression.
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DOI：
10.1182/blood-2009-08-236422
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发表时间：
2009-11
期刊：
影响因子：
20.3
通讯作者：
K. Sridhar;D. Ross;R. Tibshirani;A. Butte;P. Greenberg
中科院分区：
文献类型：
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作者：
K. Sridhar;D. Ross;R. Tibshirani;A. Butte;P. Greenberg
用40000个cDNA基因芯片芯片分析了骨髓增生异常综合征（MDS）患者和健康人的CD 34（+）骨髓细胞的差异基因表达谱（GEPs）。使用集中的生物信息学分析，我们发现1175个基因显着差异表达的MDS与正常，需要至少39个基因，分别对这些患者进行分类。在健康和MDS患者之间以及几个MDS亚组之间证实了主要的GEP差异：（1）疾病保持稳定的患者和随后转化（tMDS）为急性髓系白血病的患者;（2）del（5 q）和其他MDS患者之间。定义了一个6基因的“低风险”标记，它与急性髓性白血病转化相关，并为国际预后评分系统中间-1患者提供了额外的预后信息。在tMDS患者中证明了产生核糖体蛋白和其他信号传导途径的基因的过表达。del（5 q）与其他MDS患者的比较显示1924个差异表达基因，1014个基因表达不足，其中11个在5 q31 -32常见缺失区域内。这些数据表明：（1）GEP区分MDS患者与健康患者，以及具有不同临床结局（tMDS与疾病保持稳定的患者）和细胞遗传学[例如，del（5 q）]的患者;（2）分子标准细化MDS的预后分类和相关生物学过程。
Microarray analysis with 40 000 cDNA gene chip arrays determined differential gene expression profiles (GEPs) in CD34(+) marrow cells from myelodysplastic syndrome (MDS) patients compared with healthy persons. Using focused bioinformatics analyses, we found 1175 genes significantly differentially expressed by MDS versus normal, requiring a minimum of 39 genes to separately classify these patients. Major GEP differences were demonstrated between healthy and MDS patients and between several MDS subgroups: (1) those whose disease remained stable and those who subsequently transformed (tMDS) to acute myeloid leukemia; (2) between del(5q) and other MDS patients. A 6-gene "poor risk" signature was defined, which was associated with acute myeloid leukemia transformation and provided additive prognostic information for International Prognostic Scoring System Intermediate-1 patients. Overexpression of genes generating ribosomal proteins and for other signaling pathways was demonstrated in the tMDS patients. Comparison of del(5q) with the remaining MDS patients showed 1924 differentially expressed genes, with underexpression of 1014 genes, 11 of which were within the 5q31-32 commonly deleted region. These data demonstrated (1) GEPs distinguishing MDS patients from healthy and between those with differing clinical outcomes (tMDS vs those whose disease remained stable) and cytogenetics [eg, del(5q)]; and (2) molecular criteria refining prognostic categorization and associated biologic processes in MDS.