Abstract：
Diamond-Blackfan anemia (DBA) was the first ribosomopathy described in humans. DBA is a congenital hypoplastic anemia, characterized by macrocytic aregenerative anemia, manifesting by differentiation blockage between the BFU-e/CFU-e developmental erythroid progenitor stages. In 50 % of the DBA cases, various malformations are noted. Strikingly, for a hematological disease with a relative erythroid tropism, DBA is due to ribosomal haploinsufficiency in 24 different ribosomal protein (RP) genes. A few other genes have been described in DBA-like disorders, but they do not fit into the classical DBA phenotype (Sankaran et al., 2012; van Dooijeweert et al., 2022; Toki et al., 2018; Kim et al., 2017 [1-4]). Haploinsufficiency in a RP gene leads to defective ribosomal RNA (rRNA) maturation, which is a hallmark of DBA. However, the mechanistic understandings of the erythroid tropism defect in DBA are still to be fully defined. Erythroid defect in DBA has been recently been linked in a non-exclusive manner to a number of mechanisms that include: 1) a defect in translation, in particular for the GATA1 erythroid gene; 2) a deficit of HSP70, the GATA1 chaperone, and 3) free heme toxicity. In addition, p53 activation in response to ribosomal stress is involved in DBA pathophysiology. The DBA phenotype may thus result from the combined contributions of various actors, which may explain the heterogenous phenotypes observed in DBA patients, even within the same family.
摘要：
Diamond-Blackfan贫血（DBA）是人类中描述的第一个核糖体病。DBA是一种先天性再生障碍性贫血,以大细胞性再生性贫血为特征，表现为BFU-e/CFU-e发育红系祖细胞阶段之间的分化阻断。在50%的DBA案例中，注意到各种畸形。引人注目的是，对于具有相对红细胞样倾向的血液疾病，DBA是由于24种不同核糖体蛋白（RP）基因中的核糖体单倍体不足。在DBA样疾病中已经描述了一些其他基因，但它们不适合经典的DBA表型(Sankaran等人。,2012；vanDooijeweert等人。,2022年；Toki等人。,2018年；Kim等人。,2017年[1-4]）。RP基因中的单倍体不足导致核糖体RNA（rRNA）成熟缺陷，这是DBA的标志。然而,DBA中类红细胞嗜性缺陷的机制理解仍有待完全定义。DBA中的红系缺陷最近以非排他性的方式与许多机制相关联，这些机制包括：1）翻译中的缺陷，特别是对于GATA1类红细胞基因；2）HSP70，GATA1伴侣，3)游离血红素毒性。此外,响应核糖体应激的p53激活涉及DBA病理生理学。因此，DBA表型可能来自各种参与者的综合贡献，这可以解释在DBA患者中观察到的异质性表型，即使在同一个家庭里。
