Department of Experimental Hematology, Division of Pediatric Oncology/Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Leukemia. 2011 Dec;25(12):1825-33. doi: 10.1038/leu.2011.172. Epub 2011 Jul 15.
In order to identify acute myeloid leukemia (AML) CD34(+)-specific gene expression profiles, mononuclear cells from AML patients (n=46) were sorted into CD34(+) and CD34(-) subfractions, and genome-wide expression analysis was performed using Illumina BeadChip Arrays. AML CD34(+) and CD34(-) gene expression was compared with a large group of normal CD34(+) bone marrow (BM) cells (n=31). Unsupervised hierarchical clustering analysis showed that CD34(+) AML samples belonged to a distinct cluster compared with normal BM and that in 61% of the cases the AML CD34(+) transcriptome did not cluster together with the paired CD34(-) transcriptome. The top 50 of AML CD34(+)-specific genes was selected by comparing the AML CD34(+) transcriptome with the AML CD34(-) and CD34(+) normal BM transcriptomes. Interestingly, for three of these genes, that is, ankyrin repeat domain 28 (ANKRD28), guanine nucleotide binding protein, alpha 15 (GNA15) and UDP-glucose pyrophosphorylase 2 (UGP2), a high transcript level was associated with a significant poorer overall survival (OS) in two independent cohorts (n=163 and n=218) of normal karyotype AML. Importantly, the prognostic value of the continuous transcript levels of ANKRD28 (OS hazard ratio (HR): 1.32, P=0.008), GNA15 (OS HR: 1.22, P=0.033) and UGP2 (OS HR: 1.86, P=0.009) was shown to be independent from the well-known risk factors FLT3-ITD, NPM1c(+) and CEBPA mutation status.
为了鉴定急性髓系白血病（AML）CD34(+)特异性基因表达谱，从 AML 患者（n=46）的单核细胞中分拣出 CD34(+)和 CD34(-)亚群，并使用 Illumina BeadChip 阵列进行全基因组表达分析。AML CD34(+)和 CD34(-)基因表达与一大组正常 CD34(+)骨髓（BM）细胞（n=31）进行了比较。无监督层次聚类分析显示，与正常 BM 相比，CD34(+)AML 样本属于一个独特的簇，并且在 61%的情况下，AML CD34(+)转录组与配对的 CD34(-)转录组不聚类。通过比较 AML CD34(+)转录组与 AML CD34(-)和 CD34(+)正常 BM 转录组，选择了 AML CD34(+)特异性基因的前 50 个。有趣的是，对于其中的三个基因，即锚蛋白重复域 28（ANKRD28）、鸟嘌呤核苷酸结合蛋白，α 15（GNA15）和 UDP-葡萄糖焦磷酸化酶 2（UGP2），在两个独立的正常核型 AML 队列（n=163 和 n=218）中，高转录水平与显著较差的总体生存率（OS）相关。重要的是，ANKRD28（OS 危险比（HR）：1.32，P=0.008）、GNA15（OS HR：1.22，P=0.033）和 UGP2（OS HR：1.86，P=0.009）的连续转录水平的预后价值独立于众所周知的危险因素 FLT3-ITD、NPM1c(+)和 CEBPA 突变状态。
