Boddu Prajwal Chaitanya, Kadia Tapan Mahendra
a Department of Leukemia , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
Expert Rev Hematol. 2017 May;10(5):433-448. doi: 10.1080/17474086.2017.1313700. Epub 2017 Apr 28.
The past decade or longer has witnessed an acceleration in our understanding of previously developed immune system and clonal evolution mechanisms, and the genesis of more novel concepts of telomere attrition. Many of these concepts are steadily finding their way into translation in various aspects of clinical practice, and provide prospects to improve AA management and inform therapeutic strategy development. In this review, we intend to discuss the pathophysiology and treatments with an emphasis on most recent developments to provide an update on our understanding of disease mechanisms. Areas covered: A literature search was undertaken addressing various aspects of pathophysiology with a focus on the role of immune system repertoire, telomeres and mutational events surrounding AA. We also reviewed upon the temporal evolution of treatment strategies in AA to the contemporary management of today and commented briefly upon the more recently investigated novel therapies and their expanding niche especially in the transplant and salvage setting. Expert commentary: Immune-mediated destruction of hematopoietic stem and progenitor cells, leading to a marrow devoid of hematopoietic elements, and peripheral pancytopenia are the hallmarks of AA. Recent studies have shed light on another facet of the disease - as a clonal disorder characterized by karyotypic abnormalities, genomic instability, telomere attrition, and recurrent somatic mutations reminiscent of myeloid malignancies. Further understanding of this underlying pathophysiology can help in improving prognostication and treatment of this disease.
在过去十年或更长时间里，我们对先前已发展的免疫系统和克隆进化机制的理解加速了，同时对端粒损耗的更新颖概念也有了更多认识。其中许多概念正稳步在临床实践的各个方面得到转化，并为改善再生障碍性贫血（AA）的管理以及为治疗策略的制定提供了前景。在本综述中，我们打算讨论其病理生理学和治疗方法，重点关注最新进展，以更新我们对疾病机制的理解。涵盖领域：进行了一项文献检索，涉及病理生理学的各个方面，重点是免疫系统库、端粒以及围绕再生障碍性贫血的突变事件的作用。我们还回顾了再生障碍性贫血治疗策略从过去到当代管理的时间演变，并简要评论了最近研究的新型疗法及其不断扩大的适用范围，特别是在移植和挽救治疗方面。专家评论：免疫介导的造血干细胞和祖细胞破坏，导致骨髓缺乏造血成分以及外周全血细胞减少是再生障碍性贫血的特征。最近的研究揭示了该疾病的另一个方面——作为一种以核型异常、基因组不稳定、端粒损耗以及类似于髓系恶性肿瘤的复发性体细胞突变为特征的克隆性疾病。对这种潜在病理生理学的进一步理解有助于改善该疾病的预后和治疗。
