Inherited bone marrow failure in the pediatric patient.
Inherited bone marrow failure in the pediatric patient.
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DOI：
10.1182/blood.2020006481
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发表时间：
2022-08-11
期刊：
影响因子：
20.3
通讯作者：
Vulliamy, Tom
中科院分区：
文献类型：
--
作者：
Dokal, Inderjeet;Tummala, Hemanth;Vulliamy, Tom
由副编辑Irene Roberts和Thomas Ortel委托和介绍，本综述系列侧重于儿科血液学实践中的常见领域，强调新的治疗和诊断发展。O 'Brien和Zia描述了管理儿童止血和血栓性疾病的具体挑战。区分获得性免疫疾病和遗传性血细胞计数障碍是儿科血液学家面临的一个常见问题，Grace和Lambert对血小板减少症和Dokal等人对骨髓衰竭的综述解决了这一问题。最后，Gallagher提供了一种分步诊断和治疗婴儿期和儿童期贫血的方法，包括个体患者水平和群体水平。遗传性骨髓衰竭综合征是一组以骨髓衰竭为特征的疾病，通常伴有≥1种造血外异常。骨髓衰竭，可涉及≥1个细胞系，常出现在儿科年龄组。此外，一些最初被标记为特发性再生障碍性贫血或骨髓发育不良的儿童代表了遗传性骨髓衰竭的隐蔽性病例。在这些综合征的遗传学方面已经取得了重大进展，确定了100多个疾病基因，从而深入了解了正常的造血功能以及骨髓衰竭患者的造血功能是如何被破坏的。它们还提供了关于基本生物学途径的重要信息，包括DNA修复：范可尼贫血（FA）基因；端粒维持：先天性角化不良（DC）基因；核糖体生物发生：Shwachman-Diamond综合征和Diamond-Blackfan贫血基因。此外，由于这些疾病通常与造血外异常和癌症风险增加有关，因此它们为人类发育和癌症提供了见解。在临床上，源于最新进展的基因检测有助于诊断，特别是当临床特征不足以准确分类疾病时。使用以氟达拉滨为基础的造血干细胞移植方案可显著改善预后，特别是对于FA或DC患者。治疗其他一些并发症，如癌症，仍然是一个挑战。最近的研究表明，有可能出现新的更有效的治疗方法，包括重新关注造血基因治疗和针对疾病特异性缺陷的药物[FA和PAPD5的转化生长因子-β抑制剂，一种人聚(a)聚合酶，DC抑制剂]。
Commissioned and introduced by Associate Editors Irene Roberts and Thomas Ortel, this Review Series focuses on common areas in pediatric hematology practice, emphasizing new therapeutic and diagnostic developments. The specific challenges of managing hemostatic and thrombotic disorders in children are described by O’Brien and Zia. Distinguishing acquired immune diseases from inherited disorders of blood counts is a common problem for pediatric hematologists, and this is tackled in reviews by Grace and Lambert for thrombocytopenias and by Dokal et al for bone marrow failure. Finally, Gallagher provides a stepwise approach to the diagnosis and treatment of anemia in infancy and childhood, at both the individual patient level and the population level. Inherited bone marrow (BM) failure syndromes are a diverse group of disorders characterized by BM failure, usually in association with ≥1 extrahematopoietic abnormalities. BM failure, which can involve ≥1 cell lineages, often presents in the pediatric age group. Furthermore, some children initially labeled as having idiopathic aplastic anemia or myelodysplasia represent cryptic cases of inherited BM failure. Significant advances in the genetics of these syndromes have been made, identifying more than 100 disease genes, giving insights into normal hematopoiesis and how it is disrupted in patients with BM failure. They have also provided important information on fundamental biological pathways, including DNA repair: Fanconi anemia (FA) genes; telomere maintenance: dyskeratosis congenita (DC) genes; and ribosome biogenesis: Shwachman-Diamond syndrome and Diamond-Blackfan anemia genes. In addition, because these disorders are usually associated with extrahematopoietic abnormalities and increased risk of cancer, they have provided insights into human development and cancer. In the clinic, genetic tests stemming from the recent advances facilitate diagnosis, especially when clinical features are insufficient to accurately classify a disorder. Hematopoietic stem cell transplantation using fludarabine-based protocols has significantly improved outcomes, particularly in patients with FA or DC. Management of some other complications, such as cancer, remains a challenge. Recent studies have suggested the possibility of new and potentially more efficacious therapies, including a renewed focus on hematopoietic gene therapy and drugs [transforming growth factor-β inhibitors for FA and PAPD5, a human poly(A) polymerase, inhibitors for DC] that target disease-specific defects.
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