AGE-RELATED ALTERATIONS IN ERYTHROID AND GRANULOPOIETIC PROGENITORS IN DIAMOND-BLACKFAN ANEMIA
AGE-RELATED ALTERATIONS IN ERYTHROID AND GRANULOPOIETIC PROGENITORS IN DIAMOND-BLACKFAN ANEMIA
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DOI：
10.1111/j.1365-2141.1994.tb04924.x
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发表时间：
1994-06-01
影响因子：
6.5
通讯作者：
COULOMBEL, L
中科院分区：
文献类型：
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作者：
CASADEVALL, N;CROISILLE, L;COULOMBEL, L
以 Diamond-Blackfan 贫血 (DBA) 为特征的红细胞衰竭的机制仍不清楚。普遍的共识是，该缺陷是骨髓红细胞祖细胞固有的，但目标祖细胞尚未被精确识别，体外研究表明患者之间存在相当大的异质性。为了更好地理解这种生物异质性的含义，我们对 24 名年龄从 1 个月到 20 岁以上的患者进行了大规模系列研究，检测了红系祖细胞 CFU-E（集落形成单位 - 红系）和 BFU-E（爆发形成单位 - 红系）对促红细胞生成素 (Epo)、白细胞介素 3 (IL-3) 和干细胞因子 (SCF) 的体外反应。菌落分析结果显示，患者年龄与体外检测到的异常程度之间存在显着相关性。因此，尽管存在严重贫血，但在诊断后 1 年内研究的患者中，80% (7/10) 的 CFU-E 和 BFU-E 数量均正常，表现出对细胞因子的正常反应。相比之下，12/14 例随访超过 3 年的患者红系祖细胞数量减少，其中 7 例与粒细胞-巨噬细胞集落形成单位 (CFU-GM) 减少相关。即使添加高浓度的组合Epo、IL-3和SCF，CFU-E和BFU-E的数量也没有标准化。这些数据有力地支持了这样的观点，即 DBA 的造血缺陷涉及多能祖细胞，并随着时间的推移而恶化：它被疾病发作时的培养条件所掩盖，而内在改变的明显表达仅发生在疾病的后期阶段，并且这些不限于红系谱系。
Mechanisms involved in the erythroid failure characterizing Diamond-Blackfan anaemia (DBA) remain unidentified. The general consensus is that the defect is intrinsic to the marrow erythroid progenitor, but the target progenitor cell has not been precisely identified, and in vitro studies have revealed considerable heterogeneity between patients. In order to understand better the meaning of such a biological heterogeneity, we examined the in vitro response of erythroid progenitors CFU-E (colony-forming unit-erythroid) and BFU-E (burst-forming unit-erythroid) to erythropoietin (Epo), interleukin-3 (IL-3) and stem cell factor (SCF) in a large series of 24 patients from 1 month to over 20 years of age. Results of colony assays revealed a striking correlation between the age of the patient and the extent of the abnormalities detected in vitro. Therefore, despite profound anaemia, 80% (7/10) of the patients studied within 1 year of diagnosis had normal numbers of both CFU-E and BFU-E which exhibited a normal response to cytokines. In contrast, 12/14 patients followed up for more than 3 years had decreased numbers of erythroid progenitors, in seven cases associated with decreased colony-forming unit granulocyte-macrophage (CFU-GM). The number of CFU-E and BFU-E was not normalized even by the addition of high concentrations of combined Epo, IL-3 and SCF. These data strongly support the idea that the haemopoietic defect in DBA involves a pluripotent progenitor and worsens with time: it is masked by the culture conditions at the onset of the disease, whereas overt expression of intrinsic alterations occurs only at later stages of the disease and these are not restricted to the erythroid lineage.