Suriyun Thunwarat, Winichagoon Pranee, Fucharoen Suthat, Sripichai Orapan
Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhonpathom 73170, Thailand.
J Clin Med. 2022 Mar 22;11(7):1755. doi: 10.3390/jcm11071755.
Anemia in β-thalassemia is associated with ineffective erythropoiesis and a shortened lifespan of erythroid cells. The limited differentiation of β-thalassemic erythroblasts has been documented, but the characteristic feature of terminal erythroid maturation and its physiological relevance are not clearly described in β-thalassemias. Here, the red blood cell and reticulocyte cellular characteristics were determined in patients with β-thalassemia/HbE in comparison to patients with iron deficiency anemia and healthy normal subjects. Severely affected β-thalassemia/HbE patients showed the highest increase in immature reticulocytes, but the number of total erythrocytes was the lowest. Despite similar ranges of hemoglobin levels, β-thalassemia/HbE patients had a higher number of reticulocytes and a greater proportion of immature fraction than patients with iron deficiency anemia did. In vitro CD34 hematopoietic progenitor cells' culture and flow cytometry analysis were conducted to investigate the erythroid maturation and mitochondrial clearance in β-thalassemia/HbE erythroid cells as compared to normal cells. The delayed erythroid maturation and evidence of impaired mitochondria clearance were observed in β-thalassemia/HbE cells at the terminal stage of differentiation. Additionally, increased transcript levels of genes related to erythroid mitophagy, BNIP3L and PINK1, were revealed in β-thalassemia/HbE erythroblasts. The findings indicate that the erythroid maturation is physiologically relevant, and that the restoration of terminal maturation represents a potential therapeutic target for β-thalassemias.
β地中海贫血中的贫血与无效红细胞生成及红系细胞寿命缩短有关。β地中海贫血幼红细胞的分化受限已有文献记载，但β地中海贫血中终末红系成熟的特征及其生理相关性尚未得到明确描述。在此，对β地中海贫血/HbE患者与缺铁性贫血患者及健康正常受试者的红细胞和网织红细胞细胞特征进行了测定。重度受累的β地中海贫血/HbE患者未成熟网织红细胞增加最多，但红细胞总数最低。尽管血红蛋白水平范围相似，但β地中海贫血/HbE患者的网织红细胞数量比缺铁性贫血患者更多，未成熟比例也更高。进行了体外CD34造血祖细胞培养和流式细胞术分析，以研究β地中海贫血/HbE红系细胞与正常细胞相比的红系成熟和线粒体清除情况。在分化终末期的β地中海贫血/HbE细胞中观察到红系成熟延迟和线粒体清除受损的证据。此外，β地中海贫血/HbE幼红细胞中与红系线粒体自噬相关的基因BNIP3L和PINK1的转录水平升高。这些发现表明红系成熟具有生理相关性，终末成熟的恢复是β地中海贫血的一个潜在治疗靶点。
