Zheng Cuiling, Yang Renchi, Han Zhongchao, Zhou Bin, Liang Lu, Lu Min
State Key Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, PR China.
Crit Rev Oncol Hematol. 2008 Mar;65(3):212-22. doi: 10.1016/j.critrevonc.2007.11.003.
Megakaryocytopoiesis is a continuous developmental process of platelet production. In this process, a complex network of hemopoietic growth factors are involved, among which TPO (thrombopoietin) is the most thoroughly investigated regulator of MKs (megakaryocytes). In addition to TPO, other regulators also have non-negligible effects on megakaryocytopoiesis. The majority of their effects are independent of TPO signaling. To date, TPO-independent megakaryocytopoiesis forms a regulatory system that includes four signals and (an) unknown signaling pathway(s). These four pathways are the gp 130 (glycoprotein 130)-dependent signaling pathway, the Notch pathway, NMDA (N-methyl-d-aspartate) receptor-mediated signaling, and the SDF-1 (stromal cell-derived factor-1)/FGF-4 (fibroblast growth factor-4) paradigm. Understanding of the TPO-independent regulatory system is important because the system may offer additional opportunities to understand the developmental process and the mechanisms of disorders characterized by abnormal MK and platelet production, such as thrombocytopenia and thrombocythemia, and to advance the development of therapeutics.
巨核细胞生成是血小板产生的一个持续的发育过程。在这个过程中，涉及一个复杂的造血生长因子网络，其中血小板生成素（TPO）是对巨核细胞（MKs）研究最深入的调节因子。除了TPO，其他调节因子对巨核细胞生成也有不可忽视的作用。它们的大多数作用独立于TPO信号传导。迄今为止，不依赖TPO的巨核细胞生成形成了一个包括四个信号和未知信号通路的调节系统。这四条通路是依赖糖蛋白130（gp 130）的信号通路、Notch通路、N-甲基-D-天冬氨酸（NMDA）受体介导的信号通路以及基质细胞衍生因子-1（SDF-1）/成纤维细胞生长因子-4（FGF-4）模式。对不依赖TPO的调节系统的了解很重要，因为该系统可能为理解发育过程以及以MK和血小板生成异常为特征的疾病（如血小板减少症和血小板增多症）机制提供更多机会，并推动治疗方法发展。
