The Functional Duality of HoxB4 in Hematopoietic Reconstituting Cells
The Functional Duality of HoxB4 in Hematopoietic Reconstituting Cells
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DOI：
10.1002/cyto.a.22059
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发表时间：
2013-01-01
期刊：
影响因子：
3.7
通讯作者：
Lazarus, Hillard M.
中科院分区：
文献类型：
--
作者：
Kaplan, David;Kaye, Nicholas;Lazarus, Hillard M.
CD34(+)造血重建细胞移植是一种重要的治疗方法。临床造血重建所需的细胞最常见的来源是骨髓，这些细胞被动员到外周血中。动员血样中CD34(+)细胞的数量被用来指示移植的适宜性，尽管它没有评估成功移植所必需的两个功能：由具有自我更新增殖的细胞介导的长期重建和由祖细胞介导的短期造血细胞分化。在流式细胞仪平台上使用一种新的高分辨率免疫表型技术，我们评估了统一动员的CD34(+)细胞先前与HRC功能相关的16个分子的表达水平，并寻找这些表达数据与预测移植成功的克隆形成功能短期分析的相关性。我们发现克隆形成单位与HOXB4的表达显著相关，这可以用样本中CD34(+)细胞的数量来解释。然而，对归一化CD34(+)细胞计数的集落形成单位的分析显示，与HOXB4的表达呈显著负相关。因此，HOXB4水平的增加通过自我更新扩增增加了CD34(+)细胞的数量，但同时也降低了每个细胞的短期分化能力。我们的发现证明了将实验结果转化为临床环境，并表明CD34(+)细胞中HOXB4的表达水平可以作为样本是否适合移植的衡量标准。(C)2012年国际细胞测量促进会
Transplantation of CD34(+) hematopoietic reconstituting cells (HRC) is an important treatment modality. The cells needed for clinical hematopoietic reconstitution after myeloablation most commonly derive from bone marrow which have been mobilized into the peripheral blood. The number of CD34(+) cells in mobilized blood samples is used to indicate the appropriateness of transplantation although it does not evaluate the two necessary functions for successful transplantation: long-term reconstitution mediated by cells with self-renewing proliferation and short-term hematopoietic differentiation mediated by progenitor cells. Using a novel high-resolution immunophenotyping technology on a flow cytometric platform, we have assessed uniformly mobilized CD34(+) cells for expression levels of 16 molecules previously associated with HRC function and sought correlations of these expression data with functional short-term assays for colony formation that do predict successful transplantation. We found that colony-forming units were significantly correlated with HoxB4 expression, which was explained by the number of CD34(+) cells in the samples. However, analysis of colony-forming units normalized to the CD34(+) cell count revealed a significant negative correlation with HoxB4 expression. Thus, increased levels of HoxB4 enhance CD34(+) cell number via self-renewing expansion but concomitantly depreciate the capacity for short-term differentiation per cell. Our findings demonstrate the translation of experimental findings into a clinical setting and suggest that the expression level of HoxB4 in CD34(+) cells can be used as a measure of a sample's appropriateness for transplantation. (C) 2012 International Society for Advancement of Cytometry