Chen Z, Shivdasani R A
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
J Thromb Haemost. 2009 Jul;7 Suppl 1:272-6. doi: 10.1111/j.1538-7836.2009.03425.x.
Megakaryocyte (MK) maturation culminates in release of blood platelets through proplatelet extensions. MKs presumably delay elaborating proplatelets until synthesis of platelet constituents is complete. Recent insights from investigation of a classic human congenital macrothrombocytopenia, the May-Hegglin anomaly, and related MYH9-associated disorders shed new light on underlying mechanisms. The findings reviewed in this article implicate myosin IIA, the non-muscle myosin heavy chain product of the MYH9 gene, in restraining proplatelet formation until MKs achieve terminal maturity. Loss of myosin IIA function, through dominant inhibitory mutations in humans, targeted gene disruption in mice, or manipulation of cultured MKs, seems to accelerate proplatelet formation. The resulting process is inefficient and produces platelets that vary widely in size, shape and content. Several lines of evidence suggest that the Rho-ROCK-myosin light chain pathway restrains proplatelet formation through myosin IIA. These findings illustrate that mammalian thrombopoiesis is complex and subject to both positive and negative regulation.
巨核细胞（MK）的成熟以通过前血小板延伸释放血小板而告终。巨核细胞可能会延迟形成前血小板，直到血小板成分的合成完成。对一种典型的人类先天性血小板减少症——May-Hegglin异常以及相关的MYH9相关疾病的研究，为潜在机制带来了新的见解。本文所综述的研究结果表明，肌球蛋白IIA（MYH9基因的非肌肉肌球蛋白重链产物）在抑制前血小板形成方面发挥作用，直到巨核细胞达到终末成熟。通过人类的显性抑制性突变、小鼠的靶向基因破坏或对培养的巨核细胞进行操作，导致肌球蛋白IIA功能丧失，似乎会加速前血小板的形成。由此产生的过程效率低下，产生的血小板在大小、形状和内容物方面差异很大。几条证据表明，Rho-ROCK-肌球蛋白轻链途径通过肌球蛋白IIA抑制前血小板的形成。这些发现表明，哺乳动物的血小板生成是复杂的，并且受到正负调控。
