Differential gene expression in hematopoietic progenitors from paroxysmal nocturnal hemoglobinuria patients reveals an apoptosis/immune response in 'normal' phenotype cells

被引:31
作者
Chen, G
Zeng, W
Maciejewski, JP
Kcyvanfar, K
Billings, EM
Young, NS
机构
[1] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA
[2] NHLBI, Bioinformat Core Facil, NIH, Bethesda, MD 20892 USA
关键词
paroxysmal nocturnal hemoglobinuria (PNH); glycosylphosphatidylinositol-anchored protein (GPI-AP); gene expression; microarray;
D O I
10.1038/sj.leu.2403678
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired stem cell disorder characterized clinically by intravascular hemolysis, venous thrombosis, and bone marrow failure. Despite elucidation of the biochemical and molecular defects in PNH, the pathophysiology of clonal expansion of glycosyl-phosphatidylinositol-anchored protein (GPI-AP)-deficient cells remains unexplained. In pursuit of evidence of differences between GPI-AP-normal and - deficient CD34 cells, we determined gene expression profiles of isolated marrow CD34 cells of each phenotype from PNH patients and healthy donors, using DNA microarrays. Pooled and individual patient samples revealed consistent gene expression patterns relative to normal controls. GPI-AP-normal cells from PNH patients showed upregulation of genes involved in apoptosis and the immune response. Conversely, genes associated with antiapoptotic function and hematopoietic cell proliferation and differentiation were downregulated in these cells. In contrast, the PNH clone of GPI-AP-deficient cells appeared more similar to CD34 cells of healthy individuals. Gene chip data were confirmed by other methods. Similar gene expression patterns were present in PNH that was predominantly hemolytic as in PNH associated with aplastic anemia. Our results implicate an environmental influence on hematopoietic cell proliferation, in which the PNH clone evades immune attack and destruction, while normal cells suffer a stress response followed by programmed cell death.
引用
收藏
页码:862 / 868
页数:7
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