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

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Abstract

THE development of blood cells including expansion of megakaryocyte progenitor cells requires the interplay of marrow stromal cells and polypeptide cytokines1–10. Recently, characterization of c-Mpl, the receptor encoded by the proto-oncogene c-mpl, revealed structural homology with the haematopoietic cytokine receptor family11, and its involvement in megakaryocyte development12 We report here that the ligand for c-Mpl13 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.

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Authors and Affiliations

  1. Division of Hematology, University of Washington School of Medicine, Seattle, Washington, 98195, USA

    Kenneth Kaushansky, Virginia C. Broudy, Nancy Lin, Gerald J. Roth & Thalia Papayannopoulou

  2. ZymoGenetics Corporation, 4225 Roosevelt Way NE, Seattle, Washington, 98105, USA

    Si Lok, Richard D. Holly, Mason C. Bailey, John W. Forstrom, Michele M. Buddle, Pieter J. Oort, Fredrick S. Hagen & Donald C. Foster

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  1. Kenneth Kaushansky
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  2. Si Lok
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  3. Richard D. Holly
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  4. Virginia C. Broudy
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  5. Nancy Lin
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  6. Mason C. Bailey
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  7. John W. Forstrom
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  8. Michele M. Buddle
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  9. Pieter J. Oort
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  10. Fredrick S. Hagen
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  11. Gerald J. Roth
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  12. Thalia Papayannopoulou
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Kaushansky, K., Lok, S., Holly, R. et al. Promotion of megakaryocyte progenitor expansion and differentiation by the c-Mpl ligand thrombopoietin. Nature 369, 568–571 (1994). https://doi.org/10.1038/369568a0

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