无效红细胞生成
红细胞生成
地中海贫血
疾病
医学
贫血
生物信息学
遗传增强
β地中海贫血
转基因
计算生物学
生物
免疫学
重症监护医学
基因
遗传学
内科学
作者
Antonella Nai,Celia Cordero-Sánchez,Emanuele Tanzi,Alessia Pagani,Laura Silvestri,Simona Maria Di Modica
标识
DOI:10.1016/j.bcmd.2023.102761
摘要
β-Thalassemia is a genetic form of anemia due to mutations in the β-globin gene, that leads to ineffective and extramedullary erythropoiesis, abnormal red blood cells and secondary iron-overload. The severity of the disease ranges from mild to lethal anemia based on the residual levels of globins production. Despite being a monogenic disorder, the pathophysiology of β-thalassemia is multifactorial, with different players contributing to the severity of anemia and secondary complications. As a result, the identification of effective therapeutic strategies is complex, and the treatment of patients is still suboptimal. For these reasons, several models have been developed in the last decades to provide experimental tools for the study of the disease, including erythroid cell lines, cultures of primary erythroid cells and transgenic animals. Years of research enabled the optimization of these models and led to decipher the mechanisms responsible for globins deregulation and ineffective erythropoiesis in thalassemia, to unravel the role of iron homeostasis in the disease and to identify and validate novel therapeutic targets and agents. Examples of successful outcomes of these analyses include iron restricting agents, currently tested in the clinics, several gene therapy vectors, one of which was recently approved for the treatment of most severe patients, and a promising gene editing strategy, that has been shown to be effective in a clinical trial. This review provides an overview of the available models, discusses pros and cons, and the key findings obtained from their study.
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