St George's University of London, London, United Kingdom.
Hematology Am Soc Hematol Educ Program. 2011;2011:487-91. doi: 10.1182/asheducation-2011.1.487.
Mutations affecting genes encoding ribosomal proteins cause Diamond Blackfan anemia (DBA), a rare congenital syndrome associated with physical anomalies, short stature, red cell aplasia, and an increased risk of malignancy. p53 activation has been identified as a key component in the pathophysiology of DBA after cellular and molecular studies of knockdown cellular and animal models of DBA and other disorders affecting ribosomal assembly or function. Other potential mechanisms that warrant further investigation include impaired translation as the result of ribosomal insufficiency, which may be ameliorated by leucine supplementation, and alternative splicing leading to reduced expression of a cytoplasmic heme exporter, the human homolog of the receptor for feline leukemia virus C (FVLCR). However, the molecular basis for the characteristic steroid responsiveness of the erythroid failure in DBA remains unknown. This review explores the clinical and therapeutic implications of the current state of knowledge and delineates important but as-yet-unanswered questions.
核糖体蛋白基因的突变会导致 Diamond Blackfan 贫血（DBA），这是一种罕见的先天性综合征，与身体异常、身材矮小、红细胞生成障碍和恶性肿瘤风险增加有关。在对 DBA 及其他影响核糖体组装或功能的疾病的细胞和动物模型进行细胞和分子研究后，发现 p53 激活是 DBA 病理生理学的关键组成部分。其他需要进一步研究的潜在机制包括核糖体不足导致的翻译受损，这可以通过补充亮氨酸得到改善，以及导致细胞质血红素输出器表达减少的选择性剪接，该输出器是猫白血病病毒 C 受体（FVLCR）的人类同源物。然而，DBA 中红细胞衰竭的特征性类固醇反应的分子基础仍不清楚。这篇综述探讨了当前知识状况的临床和治疗意义，并阐述了重要但尚未得到解答的问题。
