Sugimori Chiharu, List Alan F, Epling-Burnette Pearlie K
Immunology Program and Malignant Hematology Division, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Hematol Rep. 2010 Jan 26;2(1):e1. doi: 10.4081/hr.2010.e1.
Myelodysplastic syndrome (MDS) represents one of the most challenging health-related problems in the elderly. Characterized by dysplastic morphology in the bone marrow in association with ineffective hematopoiesis, pathophysiological causes of this disease are diverse including genetic abnormalities within myeloid progenitors, altered epigenetics, and changes in the bone marrow microenvironment. The concept that T-cell mediated autoimmunity contributes to bone marrow failure has been widely accepted due to hematologic improvement after immunosuppressive therapy (IST) in a subset of patients. Currently, IST for MDS primarily involves anti-thymocyte globulin (ATG)-based regimens in which responsiveness is strongly associated with younger (under 60 years) age at disease onset. In such cases, progressive cytopenia may occur as a consequence of expanded self-reactive CD8(+) cytotoxic T lymphocytes (CTLs) that suppress hematopoietic progenitors. Although most hematologists agree that IST can offer durable hematologic remission in younger patients with MDS, an international clinical study and a better understanding of the molecular mechanisms contributing to the expansion of self-reactive CTLs is crucial. In this review, data accumulated in the US, Europe, and Asia will be summarized to provide insight and direction for a multi-center international trial.
骨髓增生异常综合征（MDS）是老年人面临的最具挑战性的健康相关问题之一。其特征为骨髓发育异常形态伴无效造血，该疾病的病理生理原因多种多样，包括髓系祖细胞内的基因异常、表观遗传学改变以及骨髓微环境变化。由于一部分患者在接受免疫抑制治疗（IST）后血液学得到改善，T细胞介导的自身免疫导致骨髓衰竭这一概念已被广泛接受。目前，MDS的IST主要涉及以抗胸腺细胞球蛋白（ATG）为基础的方案，其中反应性与疾病发病时较年轻（60岁以下）的年龄密切相关。在这种情况下，进行性血细胞减少可能是由于抑制造血祖细胞的自身反应性CD8(+)细胞毒性T淋巴细胞（CTL）扩增所致。尽管大多数血液学家都认为IST可以使年轻的MDS患者获得持久的血液学缓解，但一项国际临床研究以及对导致自身反应性CTL扩增的分子机制有更好的理解至关重要。在这篇综述中，将总结在美国、欧洲和亚洲积累的数据，为多中心国际试验提供见解和方向。
