PMID: 7536928Apr 11, 1995Paper

Thrombopoietin, the Mp1 ligand, is essential for full megakaryocyte development

Proceedings of the National Academy of Sciences of the United States of America
K KaushanskyC Lofton-Day

Abstract

The development of megakaryocytes (MKs) from their marrow precursors is one of the least understood aspects of hematopoiesis. Current models suggest that early-acting MK colony-stimulating factors, such as interleukin (IL) 3 or c-kit ligand, are required for expansion of hematopoietic progenitors into cells capable of responding to late-acting MK potentiators, including IL-6 and IL-11. Recently, the Mp1 ligand, or thrombopoietin (Tpo), has been shown to display both MK colony-stimulating factor and potentiator activities, at potencies far greater than that of other cytokines. In light of these findings, we tested the hypothesis that Tpo is absolutely necessary for MK development. In this report we demonstrate that neutralizing the biological activity of Tpo eliminates MK formation in response to c-kit ligand, IL-6, and IL-11, alone and in combination, but that these reagents only partially reduce MK formation in the presence of combinations of cytokines including IL-3. However, despite the capacity of IL-3 to support the proliferation and initial stages of MK differentiation, elimination of Tpo prevents the full maturation of IL-3-induced MK. These data indicate that two populations of MK progenitors can be identified: one that...Continue Reading

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Citations

Oct 31, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·M Peck-RadosavljevicP Ferenci
Jul 27, 2001·Journal of Cellular Physiology·C E CarowK Kaushansky
Oct 10, 1998·Stem Cells·T KatoH Miyazaki
May 20, 1998·Biotherapy·G C AvanziG Saglio
Sep 1, 1996·Leukemia Research·K Kaushansky
Dec 25, 2003·Cytokine·Virginia C Broudy, Nancy L Lin
May 9, 2002·Biochimica Et Biophysica Acta·Diana F SabathVirginia C Broudy
Nov 8, 2001·Experimental Hematology·A SchmittE M Cramer
Oct 31, 2003·Experimental Hematology·Hédia ChagraouiFrançoise Wendling
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Mar 1, 1997·Trends in Endocrinology and Metabolism : TEM·K Kaushansky
Nov 1, 1996·Trends in Cardiovascular Medicine·K Kaushansky
Feb 1, 1997·Nature Medicine·S D Nimer
Apr 12, 2000·British Journal of Haematology·R MiyazakiY Kobayashi
Feb 13, 2001·British Journal of Haematology·A MathurJ Erusalimsky
Jul 27, 2001·British Journal of Haematology·C C FolmanA E von dem Borne
Apr 12, 2003·Seminars in Hematology·Kenneth Kaushansky
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Sep 1, 2011·Tissue Engineering. Part C, Methods·Larry C Lasky, Brent Sullenbarger

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