Promotion of megakaryocyte progenitor expansion and differentiation by the c-Mpl ligand thrombopoietin

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.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Antigens, Differentiation / metabolism
  • Bone Marrow Cells
  • Cell Differentiation
  • Cell Line
  • Humans
  • Ligands
  • Megakaryocytes / cytology*
  • Mice
  • Neoplasm Proteins*
  • Proto-Oncogene Proteins
  • Receptors, Cytokine*
  • Receptors, Immunologic / metabolism*
  • Receptors, Thrombopoietin
  • Spleen / cytology
  • Thrombopoietin / metabolism*


  • Antigens, Differentiation
  • Ligands
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Receptors, Cytokine
  • Receptors, Immunologic
  • Receptors, Thrombopoietin
  • MPL protein, human
  • Thrombopoietin
  • Acetylcholinesterase