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Thromb Haemost 1995; 74(01): 521-525
DOI: 10.1055/s-0038-1642732
Symposium
Thrombopoietin
Schattauer GmbH Stuttgart

Thrombopoietin: the Primary Regulator of Megakaryocyte and Platelet Production

Kenneth Kaushansky
Division of Hematology RM-10, University of Washington Seattle, WA, USA
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Publication Date:
09 July 2018 (online)

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  • 1 Debili N, Masse J-M, Katz A, Guichard J, Breton-Gorius J, Vainchenker W. Effects of the recombinant hematopoietic growth factors interleukin-3, interieukin-6, stem cell factor, and leukemia inhibitory factor on the megakaryocytic differentiation of CD34+. cells Blood 1993; 82: 84-95
    PubMedSearch in Google Scholar
  • 2 Segal GM, Stueve T, Adamson J W. Analysis of murine megakaryocyte colony size and ploidy:Effects of interleukin-3. J Cell Physiol 1988; 137: 537-544
    CrossrefPubMedSearch in Google Scholar
  • 3 Briddell RA, Bruno E, Cooper RJ, Brandt JE, Hoffman R. Effect of c-kit ligand on in vitro human megakaryocytopoiesis. Blood 1991; 78: 2854-2859
    PubMedSearch in Google Scholar
  • 4 Avraham H, Vannier E, Cowley S, Jiang S, Chi S, Dinarello CA, Zsebo KM, Groopman JE. Effects of the stem cell factor, c-kit ligand, on human megakaryocytic cells. Blood 1992; 79: 365-371
    PubMedSearch in Google Scholar
  • 5 Kaushansky K, O’Hara RJ, Berkner K, Segal GM, Hagen FS, Adamson JW. Genomic cloning, characterization and multilineage growth -promoting activity of human granulocyte-macrophage colony-stimulating factor. Proc Nad Acad Sci USA 1986; 83: 3101-3105
    CrossrefPubMedSearch in Google Scholar
  • 6 Hirayama F, Shih J- P, Awgulewitsch A, Warr GW, Clark SC, Ogawa M. Clonal proliferation of murine lymphohemopoietic progenitors in culture. Proc Natl Acad Sci USA 1992; 89: 5907-5911
    CrossrefPubMedSearch in Google Scholar
  • 7 Hill RJ, Levin J. Regulators of thrombopoiesis:Their biochemistry and physiology. Blood Cells 1989; 15: 141-166
    PubMedSearch in Google Scholar
  • 8 McDonald TP. Thrombopoietin:Its biology, purification, and characterization. Exp Hematol 1988; 16: 201-205
    PubMedSearch in Google Scholar
  • 9 Hill RJ, Levin J, Levin FC. Correlation of in vitro and in vivo biological activities during the partial purification of thrombopoietin. Exp Hematol 1992; 20: 354-360
    PubMedSearch in Google Scholar
  • 10 Carter CD, Schultz W, McDonald TP. Thrombopoietin from human embryonic kidney cells stimulates an increase in megakaryocyte size of sublthally irradiated mice. Radiation Res 1993; 135: 32-39
    CrossrefPubMedSearch in Google Scholar
  • 11 Ishabashi T, Kimura H, Uchida T, Kariyone S, Friese P, Burstein SA. Human interleukin 6 is a direct promoter of maturation of megakaryocytes in vitro. Proc Nad Acad Sci USA 1989; 86: 5953-5957
    CrossrefPubMedSearch in Google Scholar
  • 12 Quesenberry PJ, McGrath HE, Williams ME, Robinson BE, Deacon DH, Clark S, Urdal D, McNiece IK. Multifactor stimulation of megakaryocytopoiesis :Effects of interleukin 6. Exp Hematol 1991; 19: 35-41
    PubMedSearch in Google Scholar
  • 13 Paul SR, Bennett F, Calvetti J A, Kelleher K, Wood CR, O’Hara Jr RM, Leary AC, Sibley B, Clark SC, Williams DA, Yang Y-C. Molecular cloning of a cDNA encoding interleukin 11, a stromal cell-derived lymphopoietic and hematopoietic cytokine. Proc Nad Acad Sci USA 1990; 87: 7512-7516
    CrossrefPubMedSearch in Google Scholar
  • 14 Kimura H, Ishibashi T, Uchida T, Mamyama Y, Friese P, Burstein SA. Interleukin 6 is a differentiation factor for human megakaryocytes in vitro. Eur J Immunol 1990; 20: 1927-1931
    CrossrefPubMedSearch in Google Scholar
  • 15 Burstein SA, Mei R- L, Henthom J, Friese P, Turner K. Leukemia inhibitory factor and interleukin-11 promote maturation of murine and human megakaryocytes in vitro. J Cell Physiol 1992; 153: 305-12
    CrossrefPubMedSearch in Google Scholar
  • 16 Metcalf D, Waring P, Nicola NA. Actions of leukaemia inhibitory factor on megakaryocyte and platelet formation. Ciba Foundation Symposium 1992; 167: 174-87
    PubMedSearch in Google Scholar
  • 17 Souyri M, Vigon I, Penciolelli J-F, Heard J-M, Tambourin P, Wendling F. A putative truncated cytokine receptor gene transduced by the myeloproliferative leukemia vims immortalizes hematopoietic progenitors. Cell 1990; 63: 1137-47
    CrossrefPubMedSearch in Google Scholar
  • 18 Vigon I, Momon J-P, Cocault L, Mitjavila M-T, Tambourin P, Gisselbrecht S, Souyri M. Molecular cloning and characterization of MPL, the human homolog of the v-mpl oncogene:Identification of a member of the hematopoietic growth factor receptor superfamily. Proc Natl Acad Sci USA 1992; 89: 5640-44
    CrossrefPubMedSearch in Google Scholar
  • 19 Cosman D. The hematopoietin receptor superfamily. Cytokine 1993; 5: 95-106
    CrossrefPubMedSearch in Google Scholar
  • 20 Kishimoto T, Taga T, Akira S. Cytokine signal transduction. Cell 1994; 76: 253-62
    CrossrefPubMedSearch in Google Scholar
  • 21 Murakami M, Namzaki M, Masahiko H, Yawata H, Yasukawa K, Hamaguchi M, Taga T, Kishimoto T. Critical cytoplasmic region of the interleukin 6 signal transducer gpl30 is conserved in the cytokine receptor family. Proc Nad Acad Sci USA 1991; 88: 11349-53
    CrossrefPubMedSearch in Google Scholar
  • 22 Martin P, Papayannopoulou T. HEL cells:A new human erythroleukemia cell line with spontaneous and induced globin expression. Science 1992; 216: 1233-35
    PubMedSearch in Google Scholar
  • 23 Long MW, Heffner CH, Williams JL, Peters C, Prochownik EV. Regulation of megakaryocyte phenotype in human erythroleukemia cells. J Clin Invest 1990; 85: 1072-84
    CrossrefPubMedSearch in Google Scholar
  • 24 Vigon I, Dreyfus F, Melle J, Viguie F, Ribrag V, Cocault L, Souyri M, Gisselbrecht S. Expression of the c-mpl proto-oncogene in human hematologic malignancies. Blood 1993; 82: 877-83
    PubMedSearch in Google Scholar
  • 25 Skoda RC, Seldin DC, Chiang M-K, Peichel CL, Vogt TF, Leder P. Murine c-mpl:a member of the hematopoietic growth factor receptor superfamily that transduces a proliferative signal. EMBO J 1993; 12: 2645-53
    PubMedSearch in Google Scholar
  • 26 Methia N, Louache F, Vainchenker W, Wendling F. Oligodeoxynucleotides antisense to the proto-oncogene c-mpl specifically inhibit in vitro megakaryocytopoiesis. Blood 1993; 82: 1395-1401
    PubMedSearch in Google Scholar
  • 27 Lok S, Kaushansky K, Holly RD, Kuijper JL, Lofton-Day CE, Oort PJ, Grant FJ, Helpel MD, Burkhead SK, Kramer JM, Bell LA, Sprecher CA, Blumberg H, Johnson R, Prunkard D, Ching AF T, Mathewes S L, Bailey MC, Forstrom JW, Buddie MM, Osborn SG, Evans SJ, Sheppard PO, Presnell SR, O’Hara PJ, Hagen FS, Roth GJ, Foster DC. Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo. Nature 1994; 369: 565-68
    CrossrefPubMedSearch in Google Scholar
  • 28 de Sauvage FJ, Hass PE, Spencer SD, Malloy BE, Gumey AL, Spencer SA, Darbonne WC, Henzel WJ, Wong SC, Kuang W-J, Oles KJ, Hultgren B, Solberg Jr. LA, Goeddel DV, Eaton DL. Stimulation of megakaiyocytopoiesis and thrombopoiesis by the c-Mpl ligand. Nature 1994; 369: 533-38
    CrossrefPubMedSearch in Google Scholar
  • 29 Bartley TD, Bogenberger J, Hunt P, Li Y-S, Lu H S, Martin F, Chang M-S, Samal B, Nichol JL, Swift S, Johnson MJ, Hsu R-Y, Parker VP, Suggs S, Skrine JD, Merewether LA, Clogston C, Hsu E, Hokom MM, Homkohl A, Choi E, Pangelinan M, Sun Y, Mar V, McNinch J, Simonet L, Jacobsen F, Xie C, Shutter J, Chute H, Basu R, Selander L, Trollinger D, Sieu L, Padilla D, Trail G, Elliott G, Izumi R, Covey T, Crouse J, Garcia A, Xu W, Del Castillo J, Biron J, Cole S, Hu MC-T, Pacifici R, Ponting I, Saris C, Wen D, Yung YP, Lin H, Bosselman RA. Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor Mpl. Cell 1994; 77: 1117-24
    CrossrefPubMedSearch in Google Scholar
  • 30 Sohma Y, Akahori H, Seki N, Hori T, Ogami K, Kato T, Shimada Y, Kawamura K, Miyazaki H. Molecular cloning and chromosomal localization of the human thrombopoietin gene. FEBS Letters 1994; 353: 57-61
    CrossrefPubMedSearch in Google Scholar
  • 31 Kuter DJ, Beeler DL, Rosenberg RD. The purification and physiological characteristics of ovine thrombopoietin. Blood 1994; 84 Suppl (Suppl. 01) 242a (abstr)
    PubMedSearch in Google Scholar
  • 32 Kaushansky K, Lok S, Holly RD, Broudy VC, Lin N, Bailey MC, Forstrom JW, Buddie MM, Oort PJ, Hagen FS, Roth GJ, Papayannopoulou T, Foster DC. Promotion of megakaryocyte progenitor expansion and differentiation by the c-Mpl ligand thrombopoietin. Nature 1994; 369: 568-71
    CrossrefPubMedSearch in Google Scholar
  • 33 Kaushansky K, Broudy VC, Lin N, Jorgensen M, McCarty J, Fox N, Zucker-Franklin D, Lofton-Day C. Thrombopoietin, the MPL ligand, is essential for full megakaryocyte development. (in press)
    PubMed
  • 34 Wendling F, Maraskovsky E, Debili N, Florindo C, Teepe M, Titeux M, Methia N, Breton-Gorius J, Cosman D, Vainchenker W. c-Mpl ligand is a humoral regulator of megakaryocytopoiesis. Nature 1994; 369: 571-74
    CrossrefPubMedSearch in Google Scholar
  • 35 Choi E, Nichol J, Hokom M, Homkohl A, Hunt P. Recombinant human MGDF (rhuMGDF), a ligand for c-Mpl, produces functional platelets from megakaryocytes in vitro. Blood 1994; 84 Suppl (Suppl. 01) 242a (abstr)
    PubMedSearch in Google Scholar
  • 36 Broudy VC, Lin N, Kaushansky K. Thrombopoietin (c-mpl ligand) acts synergistically with erythropoietin and stem cell factor to enhance murine megakaryocyte colony growth and increases megakaryocyte polyploidy in vitro. Blood 1994; 84 Suppl (Suppl. 01) 33Qa (abstr)
    PubMedSearch in Google Scholar
  • 37 Levin J, Levin FC, Metcalf D. The effects of acute thrombocytopenia on megakaryocyte-CFC and granulocyte-macrophage-CFC in mice:Studies of bone marrow and spleen. Blood 1980; 56: 274-83
    PubMedSearch in Google Scholar
  • 38 Gurney AL, Carver-Moore K, de Sauvage FJ, Moore MW. Thrombocytopenia in c-mpl-deficient mice. Science 1994; 265: 1445-47
    CrossrefPubMedSearch in Google Scholar
  • 39 Sprugel KH, Humes JM, Grossman A, Ren HP, Kaushansky K. Recombinant thrombopoietin stimulates rapid platelet recovery in thrombocytopenic mice. Blood 1994; 84 Suppl (Suppl. 01) 242a abstr
    PubMedSearch in Google Scholar
  • 40 Hunt P, Hokom M, Dwyer E, Faust J, del Castillo J, Chen J, Knutden A, Li Y-S, Bartley T, Bogenberger J, Homkohl A, Choi E, Nichol J, Toombs C, Sheridan C, Bosselman R, Ulich T. Megakaryocyte growth and development factor (MGDF) is a potent, physiological regulator of platelet production in normal and myelocompromised animals. Blood 1994; 84 Suppl (Suppl. 01) 390a abstr
    PubMedSearch in Google Scholar
  • 41 Ballmaeir M, Bogenberger J, Shutter J, Welcher A, Tidow N, Konig A, Wilken Av, Schweinitz D, Hadam M, Welte K. Analysis of expression of megakaryocyte growth and development factor mRNA in various human normal and malignant tissues. Blood. 1994
    PubMedSearch in Google Scholar
  • 42 McCarty JM, Kaushansky K. Murine thrombopoietin mRNA levels are modulated by platelet count. Blood 1994; 84 Suppl (Suppl. 01) 241a abstr
    PubMedSearch in Google Scholar
  • 43 Heaney ML, Golde DW. Soluble hormone receptors. Blood 1993; 82: 1945-1948
    PubMedSearch in Google Scholar