Kaushansky K, Lok S, Holly R D, Broudy V C, Lin N, Bailey M C, Forstrom J W, Buddle M M, Oort P J, Hagen F S
Division of Hematology, University of Washington School of Medicine, Seattle 98195.
Nature. 1994 Jun 16;369(6481):568-71. doi: 10.1038/369568a0.
The development of blood cells including expansion of megakaryocyte progenitor cells requires the interplay of marrow stromal cells and polypeptide cytokines. Recently, characterization of c-Mpl, the receptor encoded by the proto-oncogene c-mpl, revealed structural homology with the haematopoietic cytokine receptor family, and its involvement in megakaryocyte development. We report here that the ligand for c-Mpl is relatively lineage specific, works both alone and synergistically with early acting cytokines to support megakaryocyte colony formation, and acts at a late stage of development to increase megakaryocyte size, polyploidization and expression of differentiation markers. In vivo, c-Mpl ligand stimulates platelet production by greatly expanding marrow and splenic megakaryocytes and their progenitors, and by shifting the distribution of megakaryocyte ploidy to higher values. Thus, as c-Mpl ligand has the expected characteristics of the major regulator of megakaryocyte development, we propose that it be termed thrombopoietin.
血细胞的发育，包括巨核细胞祖细胞的扩增，需要骨髓基质细胞和多肽细胞因子的相互作用。最近，原癌基因c-mpl编码的受体c-Mpl的特性揭示了其与造血细胞因子受体家族的结构同源性，以及它在巨核细胞发育中的作用。我们在此报告，c-Mpl的配体具有相对的谱系特异性，它既能单独发挥作用，也能与早期作用的细胞因子协同作用，以支持巨核细胞集落形成，并在发育后期发挥作用，增加巨核细胞的大小、多倍体化以及分化标志物的表达。在体内，c-Mpl配体通过极大地扩增骨髓和脾脏中的巨核细胞及其祖细胞，并将巨核细胞倍性分布转向更高值，从而刺激血小板生成。因此，由于c-Mpl配体具有巨核细胞发育主要调节因子的预期特性，我们建议将其命名为血小板生成素。
