Hematology Service, Oncology Center, Hospital São Jose, Beneficência Portuguesa, Rua Martiniano de Carvalho, 951, São Paulo, SP 01321-001, Brazil.
Int J Hematol. 2013 May;97(5):553-7. doi: 10.1007/s12185-013-1332-x. Epub 2013 May 1.
The decision to pursue hematopoietic stem cell transplantation or immunosuppression as first therapy in severe aplastic anemia is currently based on age and availability of a histocompatible donor. The ability to predict hematologic response, relapse and clonal evolution could improve treatment allocation. In the past 15 years, telomeres have been implicated in clinical diseases such as aplastic anemia, pulmonary fibrosis, cirrhosis and cancer development. The clinical relevance of varying telomere lengths (TL) and/or mutations in genes of the telomerase complex (TERC, TERT) is evolving in aplastic anemia. A large retrospective analysis suggests that baseline TL associate with late events of hematologic relapse and clonal evolution in aplastic anemia patients treated initially with anti-thymocyte globulin-based therapy. Further laboratory experiments propose possible mechanistic insight into genomic instability of bone marrow cells derived from patients with critically short telomeres and/or mutation in telomerase genes. The possibility of modulating telomere attrition rate with sex hormones could positively affect clonal evolution rates in humans. This review will summarize studies in marrow failure that explore the association between telomeres and aplastic anemia outcomes.
目前，在重型再生障碍性贫血中，选择进行造血干细胞移植或免疫抑制治疗作为一线治疗，主要依据年龄和是否存在组织相容性供体。如果能够预测血液学反应、复发和克隆演变，就可以改善治疗方案的分配。在过去的 15 年中，端粒已被认为与多种临床疾病有关，如再生障碍性贫血、肺纤维化、肝硬化和癌症发展。端粒长度（TL）的变化和/或端粒酶复合物（TERC、TERT）基因的突变在再生障碍性贫血中的临床相关性正在不断发展。一项大型回顾性分析表明，在接受抗胸腺细胞球蛋白为基础的治疗的再生障碍性贫血患者中，基线 TL 与血液学复发和克隆演变的晚期事件相关。进一步的实验室实验提出了可能的机制见解，即源自端粒严重缩短和/或端粒酶基因突变的患者的骨髓细胞的基因组不稳定性。通过性激素调节端粒损耗率，可能会对人类的克隆演变率产生积极影响。本综述将总结探讨端粒与再生障碍性贫血结局之间关联的骨髓衰竭相关研究。
