Sun Rui-Jie, Shan Ning-Ning
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, 325 Jing Wu Rd, Jinan, 250021 Shandong People's Republic of China.
Cancer Cell Int. 2019 Mar 15;19:59. doi: 10.1186/s12935-019-0779-0. eCollection 2019.
Immune thrombocytopenic purpura (ITP) is a multifactorial autoimmune disease characterized by both increased platelet destruction and/or reduced platelet production. Even though they are detected in ≤ 50% of ITP patients, auto-antibodies play a pivotal role in the pathogenesis of ITP. Recent experimental and clinical observations have revealed abnormal autophagy in ITP patients. Autophagy is a catabolic process responsible for the elimination and recycling of cytoplasmic constituents, such as organelles and macromolecules, in eukaryotic cells. Additionally, it triggers cell death or promotes cell survival following various forms of stress, and maintains the microenvironment and stemness of haematopoietic stem cells. The role of autophagy in megakaryopoiesis, thrombopoiesis, and platelet function is slowly being uncovered. The abnormal autophagy in ITP patients may be caused by deletion of autophagy-related genes such as ATG7 and abnormal signalling due to overexpression of mTOR. These changes are thought to affect markers of haematopoietic stem cells, such as CD41 and CD61, and differentiation of megakaryocytes, ultimately decreasing the function and quantity of platelets and leading to the onset of ITP. This review highlights recent evidence on the essential role played by autophagy in megakaryopoiesis, megakaryocyte differentiation, thrombopoiesis, and platelet production. It also discusses the potential of targeting the autophagy pathway as a novel therapeutic approach against ITP.
免疫性血小板减少性紫癜（ITP）是一种多因素自身免疫性疾病，其特征为血小板破坏增加和/或血小板生成减少。尽管在≤50%的ITP患者中可检测到自身抗体，但自身抗体在ITP的发病机制中起关键作用。最近的实验和临床观察揭示了ITP患者存在自噬异常。自噬是一种分解代谢过程，负责真核细胞中细胞质成分（如细胞器和大分子）的清除和再循环。此外，它在各种形式的应激后触发细胞死亡或促进细胞存活，并维持造血干细胞的微环境和干性。自噬在巨核细胞生成、血小板生成和血小板功能中的作用正逐渐被揭示。ITP患者的自噬异常可能是由于自噬相关基因（如ATG7）的缺失以及mTOR过度表达导致的信号异常。这些变化被认为会影响造血干细胞标志物（如CD41和CD61）以及巨核细胞的分化，最终降低血小板的功能和数量，导致ITP的发病。本综述重点介绍了自噬在巨核细胞生成、巨核细胞分化、血小板生成和血小板产生中所起重要作用的最新证据。它还讨论了将自噬途径作为治疗ITP的一种新治疗方法的潜力。
