Diamond Blackfan anemia: a Cheshire cat of hematology.
Diamond Blackfan anemia: a Cheshire cat of hematology.
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戴蒙德·布莱克凡贫血症：血液学的柴郡猫。
DOI：
10.1002/pbc.25014
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发表时间：
2014
影响因子：
3.2
通讯作者：
Farrar,JasonE
中科院分区：
文献类型：
--
作者：
Farrar,JasonE
钻石布莱克凡贫血 (DBA) 具有神秘的起源、不可预测的血液学组合、顽固不化（导致皮质类固醇或输血相关毒性）、反复无常的缓解、广泛但潜在微妙的身体异常以及癌症易感综合征的潜在恶意，四代多代以来，钻石布莱克范贫血 (DBA) 既让血液学家烦恼又着迷。尽管 DBA 的许多方面仍然是个谜，但过去 15 年加速进行的仔细实验室和临床研究，在提高我们对 DBA 遗传起源的理解方面取得了实质性进展。在最初发现儿童携带核糖体小亚基易位破坏成分后，一系列研究表明核糖体是 DBA 的常见罪魁祸首。目前，DBA 中已识别出常染色体显性突变或单拷贝缺失，涉及至少 11 个编码核糖体蛋白 (RP) 的基因，这些基因是核糖体蛋白的小亚基（表示为“RPS”—RPS7、RPS10、RPS17、RPS19、RPS24 和 RPS26）或大亚基（表示为“RPL”—RPL5、RPL11、RPL15、RPL26 和 RPL35A）的组成部分。 [1-4]回想起来，这些发现与其他遗传性骨髓衰竭综合征的发现有相似之处，人们认识到一大群相关的基因在共同的生物途径上交叉，例如范可尼贫血中的DNA修复途径或先天性角化不良和相关疾病中的端粒维持途径。然而，在 DBA 中，本论文也出现了潜在失败的令人不安的迹象。虽然针对核糖体所有已知结构成分的一系列测序研究发现了新的 DBA 基因，但这些研究还表明，大约 40% 临床诊断为 DBA 的患者没有可识别的 RP 基因异常。
With mysterious origins, an unpredictable hematological combination of intransigence—with resulting corticosteroid-or transfusion-related toxicity—and the capriciousness of remission, a broad but potentially subtle array of physical abnormalities, and the lurking malevolence of a cancer predisposition syndrome, Diamond Blackfan anemia (DBA) has both vexed and fascinated hematologists for more than four generations. Although many aspects of DBA remain enigmatic, careful laboratory and clinical investigation, accelerating over the past 15 years, have led to substantial progress in improving our understanding of the genetic origins of DBA.Following the initial discovery of a child harboring a translocation disrupting component of the small ribosomal subunit, a series of studies have shown the ribosome to be a common culprit in DBA. Autosomal dominant mutations or single copy deletions are now recognized in DBA involving at least 11 genes encoding ribosomal proteins (RP) that are components of either the small (denoted “RPS”—RPS7, RPS10, RPS17, RPS19, RPS24 and RPS26) or large (denoted “RPL”—RPL5, RPL11, RPL15, RPL26 and RPL35A) subunit of the ribosome.[1–4] In retrospect, these discoveries have followed a parallel arc to findings in other inherited bone marrow failure syndromes, with recognition that a large but related group of genes intersect at a common biological pathway, such as DNA repair pathways in Fanconi anemia or telomere maintenance pathways in dyskeratosis congenita and related disorders. In DBA however, there have also been troubling signs of potential failure in this thesis. While the flurry of sequencing studies focusing on all the known structural components of the ribosome identified novel DBA genes, these studies also suggested that approximately 40% of patients with a clinical diagnosis of DBA do not have an identifiable RP gene abnormality.