Hofmann Wolf-K, de Vos Sven, Komor Martina, Hoelzer Dieter, Wachsman William, Koeffler H Phillip
Division of Hematology/Oncology, Cedars Sinai Research Institute, Los Angeles, CA, USA.
Blood. 2002 Nov 15;100(10):3553-60. doi: 10.1182/blood.V100.10.3553.
Gene patterns of expression in purified CD34(+) bone marrow cells from 7 patients with low-risk myelodysplastic syndrome (MDS) and 4 patients with high-risk MDS were compared with expression data from CD34(+) bone marrow cells from 4 healthy control subjects. CD34(+) cells were isolated by magnetic cell separation, and high-density oligonucleotide microarray analysis was performed. For confirmation, the expression of selected genes was analyzed by real-time polymerase chain reaction. Class membership prediction analysis selected 11 genes. Using the expression profile of these genes, we were able to discriminate patients with low-risk from patients with high-risk MDS and both patient groups from the control group by hierarchical clustering (Spearman confidence). The power of these 11 genes was verified by applying the algorithm to an unknown test set containing expression data from 8 additional patients with MDS (3 at low risk, 5 at high risk). Patients at low risk could be distinguished from those at high risk by clustering analysis. In low-risk MDS, we found that the retinoic-acid-induced gene (RAI3), the radiation-inducible, immediate-early response gene (IEX1), and the stress-induced phosphoprotein 1 (STIP1) were down-regulated. These data suggest that CD34(+) cells from patients with low-risk MDS lack defensive proteins, resulting in their susceptibility to cell damage. In summary, we propose that gene expression profiling may have clinical relevance for risk evaluation in MDS at the time of initial diagnosis. Furthermore, this study provides evidence that in MDS, hematopoietic stem cells accumulate defects that prevent normal hematopoiesis.
将7例低危骨髓增生异常综合征（MDS）患者和4例高危MDS患者纯化的CD34(+)骨髓细胞中的基因表达模式，与4例健康对照者的CD34(+)骨髓细胞的表达数据进行了比较。通过磁性细胞分离法分离CD34(+)细胞，并进行高密度寡核苷酸微阵列分析。为进行验证，通过实时聚合酶链反应分析所选基因的表达。类别归属预测分析筛选出11个基因。利用这些基因的表达谱，我们能够通过层次聚类（Spearman置信度）将低危患者与高危MDS患者以及两组患者与对照组区分开来。将该算法应用于一个包含另外8例MDS患者（3例低危，5例高危）表达数据的未知测试集，验证了这11个基因的效能。通过聚类分析可将低危患者与高危患者区分开来。在低危MDS中，我们发现维甲酸诱导基因（RAI3）、辐射诱导的早期反应基因（IEX1）和应激诱导磷蛋白1（STIP1）表达下调。这些数据表明，低危MDS患者的CD34(+)细胞缺乏防御蛋白，导致其易受细胞损伤。总之，我们认为基因表达谱分析在MDS初诊时的风险评估中可能具有临床意义。此外，本研究提供了证据，表明在MDS中，造血干细胞积累了妨碍正常造血的缺陷。
