原始谱系- CD34+CD38 - CD90+CD45RA -造血干细胞/祖细胞亚群分离自脐带血,动员外周血和慢性髓性白血病患者的进一步表型表征
Further phenotypic characterization of the primitive lineage− CD34+CD38−CD90+CD45RA− hematopoietic stem cell/progenitor cell sub-population isolated from cord blood, mobilized peripheral blood and patients with chronic myelogenous leukemia
原文发布日期:2011-09-30
DOI: 10.1038/bcj.2011.35
类型: Original Article
开放获取: 是
英文摘要:
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原文链接:
The most primitive hematopoietic stem cell (HSC)/progenitor cell (PC) population reported to date is characterized as being Lin−CD34+CD38−CD90+CD45R. We have a long-standing interest in comparing the characteristics of hematopoietic progenitor cell populations enriched from normal subjects and patients with chronic myelogenous leukemia (CML). In order to investigate further purification of HSCs and for potential targetable differences between the very primitive normal and CML stem/PCs, we have phenotypically compared the normal and CML Lin−CD34+CD38−CD90+CD45RA− HSC/PC populations. The additional antigens analyzed were HLA-DR, the receptor tyrosine kinases c-kit and Tie2, the interleukin-3 cytokine receptor, CD33 and the activation antigen CD69, the latter of which was recently reported to be selectively elevated in cell lines expressing the Bcr-Abl tyrosine kinase. Notably, we found a strikingly low percentage of cells from the HSC/PC sub-population isolated from CML patients that were found to express the c-kit receptor (<1%) compared with the percentages of HSC/PCs expressing the c-kitR isolated from umbilical cord blood (50%) and mobilized peripheral blood (10%). Surprisingly, Tie2 receptor expression within the HSC/PC subset was extremely low from both normal and CML samples. Using in vivo transplantation studies, we provide evidence that HLA-DR, c-kitR, Tie2 and IL-3R may not be suitable markers for further partitioning of HSCs from the Lin−CD34+CD38−CD90+CD45RA− sub-population.
迄今为止报道的最原始造血干细胞/祖细胞群体的特征为Lin−CD34+CD38−CD90+CD45R。我们长期致力于比较正常受试者和慢性髓系白血病患者富集的造血祖细胞群体特征。为了深入研究造血干细胞的进一步纯化以及探寻原始正常干细胞与CML干细胞/祖细胞之间潜在的可靶向差异,我们通过表型分析对比了正常与CML的Lin−CD34+CD38−CD90+CD45RA− HSC/PC群体。额外分析的抗原包括HLA-DR、受体酪氨酸激酶c-kit和Tie2、白细胞介素-3细胞因子受体、CD33及激活抗原CD69(后者近期被报道在表达Bcr-Abl酪氨酸激酶的细胞系中选择性升高)。值得注意的是,我们发现从CML患者分离的HSC/PC亚群中表达c-kit受体的细胞比例极低(<1%),而脐带血(50%)和动员外周血(10%)中表达c-kitR的HSC/PC比例显著更高。出乎意料的是,在正常和CML样本的HSC/PC亚群中Tie2受体表达均极低。通过体内移植实验,我们证明HLA-DR、c-kitR、Tie2和IL-3R可能不适合作为从Lin−CD34+CD38−CD90+CD45RA−亚群中进一步分离HSC的标志物。
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