CIRCULATING BFU-E HETEROGENEITY IN SICKLE CELL ANEMIA

镰状细胞性贫血中循环 BFU-E 的异质性

• 批准号: 6241975
• 负责人: HELENA P CROIZAT
• 金额: $ 22.82万
• 依托单位: MONTEFIORE MEDICAL CENTER (BRONX, NY)
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6241975
• 关键词: antibody neutralization test; bioassay; cell cycle; cell growth regulation; colony stimulating factor; cytokine receptors; enzyme linked immunosorbent assay; erythroid stem cell; erythropoiesis; erythropoietin; flow cytometry; growth factor receptors; growth inhibitors; growth media; hematology; hematopoietic growth factor; hemoglobin F; human tissue; interleukin 3; monocyte; radioimmunoassay; sickle cell anemia; tissue /cell culture; transforming growth factors

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?

目前的建议是基于我们以前的研究， 镰状细胞性贫血患者的外周血BFU-E在其 根据HbF的外周百分比的特征。 具体而言，低HbF患者（< 9%）的BFU-E数量较高， 这些BFU-E的高比例在积极的循环和粘附 从这些患者获得的单核细胞组成性地产生 BPA。 最近的研究表明，GM-CSF是唯一的 或者说是BPA活性的最重要的组成部分。 此外，本发明还提供了一种方法， 初步数据表明， 从高HbF SS患者（> 9%）的外周血中收获， BFU-E的负生长因子。 最后，使用延迟添加 我们已经检测到EpO内在特征的异质性， SS疾病中的BFU-E：一些BFU-E仅对EpO敏感，另一些对EpO敏感。 GM-CSF和IL-3，还有一些是单独的IL-3。 异质性也 随外周血HbF水平而变化。 本提案的具体目标 以下是：BPA涉及哪些积极的增长因素 来源于影响低HbF SS患者BFU-E的贴壁细胞？ 除了GM-CSF，IL-3是否也参与其中？ 负增长因素有哪些 参与调节镰状细胞性贫血患者的BFU-E， 高HbF？是否存在GM-CSF和其他生长因子， 镰状细胞性贫血患者血液中的水平？ 这与HB有关吗 F级？使用延迟加入EpO的策略来区分 BFU-E群体根据其对EpO的不同敏感性， GM-CSF和IL-3，问：镰状细胞性贫血患者是否有 对生长因子敏感性不同的BFU-E人群？ 如果 那么，生长因子敏感性的分布是如何相互关联的呢？ HbF和SS疾病的其他血液学参数？