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首页> 外文期刊>British Journal of Haematology >Advances in megakaryocytopoiesis and thrombopoiesis: From bench to bedside
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Advances in megakaryocytopoiesis and thrombopoiesis: From bench to bedside

机译：巨核细胞生成和血小板生成的进展：从板凳到床边

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Megakaryocytopoiesis involves the commitment of haematopoietic stem cells, proliferation and terminal differentiation of megakaryocytic progenitors (MK-p) and maturation of megakaryocytes (MKs) to produce functional platelets. This complex process occurs in specialized niches in the bone marrow where MKs align adjacent to vascular endothelial cells, form proplatelet projections and release platelets into the circulation. Thrombopoietin (THPO, TPO) is the primary growth factor for the MK lineage and necessary at all stages of development. THPO is constitutively produced in the liver, and binds to MPL (c-Mpl) receptor on platelets and MKs. This activates a cascade of signalling molecules, which induce transcription factors to drive MK development and thrombopoiesis. Decreased turnover rate and platelet number result in increased levels of free THPO, which induces a concentration-dependant compensatory response of marrow-MKs to enhance platelet production. Newly developed thrombopoietic agents operating via MPL receptor facilitate platelet production in thrombocytopenic states, primarily immune thrombocytopenia. Other drugs are available for attenuating malignant thrombocytosis. Herein, we review the regulation of megakaryocytopoiesis and platelet production in normal and disease states, and the innovative drugs and therapeutic modalities to stimulate or decrease thrombopoiesis.
机译：巨核细胞生成涉及造血干细胞的承诺，巨核细胞祖细胞（MK-p）的增殖和终末分化以及巨核细胞（MKs）的成熟以产生功能性血小板。这种复杂的过程发生在骨髓中的特定部位，在这些部位中，MK与血管内皮细胞相邻排列，形成血小板前突并释放血小板进入循环系统。血小板生成素（THPO，TPO）是MK谱系的主要生长因子，在所有发育阶段都是必需的。 THPO在肝脏中组成性产生，并与血小板和MK上的MPL（c-Mpl）受体结合。这激活了一系列信号分子，这些信号分子诱导转录因子来驱动MK发育和血小板生成。周转率和血小板数量的减少导致游离THPO含量增加，从而诱导了骨髓MKs的浓度依赖性补偿反应，从而增强了血小板生成。通过MPL受体起作用的新开发的血小板生成剂可促进血小板减少状态（主要是免疫性血小板减少）中的血小板生成。其他药物可用于减轻恶性血小板增多症。本文中，我们回顾了正常和疾病状态下巨核细胞生成和血小板产生的调节，以及刺激或减少血小板生成的创新药物和治疗方法。

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