CIRCULATING BFU-E HETEROGENEITY IN SICKLE CELL ANEMIA

目前的建议是基于我们先前的研究，这些研究表明 镰状细胞性贫血患者外周血BFU-E的变化 根据HbF的外周百分比进行特征分析。 具体地说，低HBF患者(9%)，有较高数量的BFU-E， 这些BFU-E在积极骑行和附着中所占比例很高 从这些患者身上获得的单个核细胞结构性地产生 双酚A。最近的研究表明，GM-CSF要么是唯一的 也是这一双酚A活动最重要的组成部分。此外, 初步数据显示，光密度单个核细胞 从高HBF SS患者(&gt；9%)外周血中采集产生 BFU-E的负生长因子最后，使用延迟相加 我们已经检测到EPO的内在特征的异质性 BFU-E在SS病中的作用：一些BFU-E单独对EPO敏感，另一些对EPO敏感 GM-CSF和IL-3等单独作用于IL-3。异质性还包括 随着外周HBF水平的不同而变化。这项建议的具体目的 以下是：BPA涉及的积极增长因素有哪些 来自于影响低HBF SS患者BFU-E的贴壁细胞？ 除了GM-CSF外，IL-3还参与了吗？负面增长因素有哪些？ 参与镰状细胞性贫血患者BFU-E的调节 高HBF？；GM-CSF和其他生长因子在可检测到的 镰状细胞性贫血患者的血液水平？这与HB有关吗？ F水平；使用EPO延迟添加的策略来区分 根据BFU-E对EPO的差异敏感性， GM-CSF和IL-3问：镰状细胞贫血患者是否有 对生长因子具有不同敏感性的BFU-E种群？如果 那么，生长因子敏感性的分布是如何相关的呢？ 与SS病的HbF等血液学指标有关？

The present proposal is based on our previous studies which demonstrated that peripheral BFU-E in sickle cell anemia patients varied in their characteristics according to the peripheral percent of HbF. Specifically, low HbF patients (< 9%), have a higher number of BFU-E, with a high proportion of these BFU-E in active cycling and adherent mononuclear cells obtained from these patients constitutively produce BPA. More recent work has demonstrated that GM-CSF is either the sole or most important component of this BPA activity. In addition, preliminary data demonstrates that light density mononuclear cells harvested from peripheral blood of high HbF SS patients (> 9%) produce negative growth factors for BFU-E. Finally, using delayed addition of EpO we have detected heterogeneity in the intrinsic characteristics of BFU-E in SS disease: some BFU-E are sensitive to EpO alone, others to GM-CSF and IL-3 and yet others to IL-3 alone. The heterogeneity also varies with peripheral HbF levels. The SPECIFIC AIMS of this proposal are the following: What are the positive growth factors involved in BPA derived from the adherent cells that affect BFU-E in low HbF SS patients? Besides GM-CSF, is IL-3 involved? What are the negative growth factors involved in the regulation of BFU-E in sickle cell anemia patients with high HbF?; Are GM-CSF, and other growth factors, found in detectable levels in blood of sickle cell anemia patients? Is this related with HB F levels?; Using the strategy of delayed addition of EpO to distinguish populations of BFU-E according to their differential sensitivity to EpO, GM-CSF and IL-3, ask: Do patients with sickle cell anemia have populations of BFU-E with diverse sensitivities to growth factors? If so, how is the distribution of growth factor sensitivities correlated with HbF and other hematological parameters of SS disease?