Department of Transfusion Medicine and Cell Processing, Faculty of Medicine, Tokyo Women's Medical University.
Institute of Medical Genetics, Tokyo Women's Medical University.
Tohoku J Exp Med. 2021 Sep;255(1):49-55. doi: 10.1620/tjem.255.49.
Diamond-Blackfan anemia is a congenital bone marrow failure syndrome characterized by red blood cell (RBC) aplasia with varied malformations in infants. Elevated activity of adenosine deaminase (ADA) has been considered as a useful biomarker of Diamond-Blackfan anemia, and ADA assay has been shown to be more sensitive than genetic diagnosis. Approximately, 80% of the examined patients showed elevated ADA activity, whereas genetic tests of ribosome subunit genes identified mutations in approximately 60% of the patients. We previously reported that reduced glutathione (GSH) levels in RBCs may serve as a biomarker of Diamond-Blackfan anemia. In this study, to confirm the universality of our data, we extended the analysis to seven RBC enzymes and GSH of 14 patients with Diamond-Blackfan anemia and performed a cross-analysis study using enzyme activity assay and recently reported proteome data. Statistical analysis revealed that both data exhibited high similarity, upregulation in the hexokinase and pentose-phosphate pathway, and downregulation in glycolytic enzymes such as phosphofructokinase and pyruvate kinase, in the RBCs obtained from the subjects with Diamond-Blackfan anemia. The only discrepancy between enzyme activity and proteome data was observed in glucose-6-phosphate dehydrogenase (G6PD), as increased G6PD activity showed no relation with the significant elevation in protein levels. These results suggest that our enzymatic activity data of Diamond-Blackfan anemia are universal and that the enzymatic activation of G6PD via a hitherto-unveiled mechanism is another metabolic feature of RBCs of Diamond-Blackfan anemia.
先天性红系再生障碍性贫血是一种骨髓衰竭综合征，其特征是婴儿出现红细胞（RBC）再生障碍和各种畸形。腺苷脱氨酶（ADA）活性升高被认为是 Diamond-Blackfan 贫血的有用生物标志物，ADA 测定比基因诊断更敏感。大约 80%的患者表现出 ADA 活性升高，而核糖体亚基基因的遗传检测发现约 60%的患者存在突变。我们之前报道 RBC 中的还原型谷胱甘肽（GSH）水平可能作为 Diamond-Blackfan 贫血的生物标志物。在这项研究中，为了确认我们数据的普遍性，我们将分析扩展到 14 例 Diamond-Blackfan 贫血患者的 7 种 RBC 酶和 GSH，并使用酶活性测定和最近报道的蛋白质组数据进行交叉分析研究。统计分析显示，两种数据均显示出高度相似性，在 Diamond-Blackfan 贫血患者的 RBC 中，己糖激酶和戊糖磷酸途径上调，糖酵解酶如磷酸果糖激酶和丙酮酸激酶下调。酶活性和蛋白质组数据之间唯一的差异仅见于葡萄糖-6-磷酸脱氢酶（G6PD），因为 G6PD 活性增加与蛋白质水平的显著升高无关。这些结果表明，我们的 Diamond-Blackfan 贫血酶活性数据具有普遍性，通过迄今尚未揭示的机制激活 G6PD 是 Diamond-Blackfan 贫血 RBC 的另一种代谢特征。
