Diamond-blackfan anemia: in vitro response of erythroid progenitors to the ligand for c-kit.
Diamond-blackfan anemia: in vitro response of erythroid progenitors to the ligand for c-kit.
复制标题
DOI：
10.1182/blood.v78.9.2198.2198
复制
发表时间：
1991-11
期刊：
影响因子：
20.3
通讯作者：
J. Abkowitz;J. Abkowitz;K. Sabo;K. Sabo;B. Nakamoto;B. Nakamoto;C. Blau;C. Blau;Frank H. Martin-Frank-H.
中科院分区：
文献类型：
--
作者：
J. Abkowitz;J. Abkowitz;K. Sabo;K. Sabo;B. Nakamoto;B. Nakamoto;C. Blau;C. Blau;Frank H. Martin-Frank-H.
为了深入了解 Diamond-Blackfan 贫血的发病机制，我们检查了红系祖细胞对最近分离的 c-kit（干细胞因子，SCF）配体的体外反应。在这些研究中，来自 10 名 Diamond-Blackfan 患者的骨髓或血液单核细胞与促红细胞生成素 (Ep)、Ep 和白细胞介素 3、Ep 和粒细胞巨噬细胞集落刺激因子或 Ep 和淋巴细胞条件培养基 (LCM) 一起培养。这些组合在存在或不存在 SCF 的情况下进行了测试。在含有 SCF 的培养物中，每次红细胞爆发的平均细胞数增加了 5 至 50 倍。此外，还观察到许多额外的红细胞爆发（平均增量 3.2 x 基线值）。尽管所有患者的突发形成单位红细胞 (BFU-E) 都有反应，但个体之间 BFU-E 对 SCF 的敏感性存在差异。在六名患者和所有对照研究中，红细胞爆发的平台频率是在小于或等于 10 ng/mL SCF 的情况下实现的，而在其他四名患者的研究中，需要超过 50 ng/mL SCF。这些数据引发了人们的猜测：c-kit 受体/配体轴参与了 Diamond-Blackfan 贫血的发病机制。更重要的是，无论观察到的反应模式是否反映了主要缺陷或副现象，我们的数据都强烈支持对 Diamond-Blackfan 贫血患者进行 SCF 治疗试验。
To provide insights into the pathogenesis of Diamond-Blackfan anemia, we examined the in vitro response of erythroid progenitors to the recently isolated ligand for c-kit (stem cell factor, SCF). For these studies, marrow or blood mononuclear cells from 10 Diamond-Blackfan patients were cultured with erythropoietin (Ep), Ep and interleukin-3, Ep and granulocyte-macrophage colony-stimulating factor, or Ep and lymphocyte conditioned media (LCM). These combinations were tested in the presence or absence of SCF. The mean number of cells per erythroid burst increased 5 to 50-fold in cultures containing SCF. Furthermore, many additional erythroid bursts were seen (mean increment 3.2 x baseline values). Although burst-forming unit-erythroid (BFU-E) from all patients responded, there were differences among individuals in the sensitivity of their BFU-E to SCF. In six patients and all control studies, plateau frequencies of erythroid bursts were achieved with less than or equal to 10 ng/mL SCF, whereas in studies from the other four patients, over 50 ng/mL SCF was required. These data invite speculation that the c-kit receptor/ligand axis is involved in the pathogenesis of Diamond-Blackfan anemia. More importantly and regardless of whether the observed patterns of response reflect the primary defect or an epiphenomenon, our data strongly support a therapeutic trial of SCF in patients with Diamond-Blackfan anemia.