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Thromb Haemost 1995; 74(01): 204-209
DOI: 10.1055/s-0038-1642677
Symposium
Megakaryocytes
Schattauer GmbH Stuttgart

Megakaryocytopoiesis: The State of the Art

Alan M Gewirtz
Departments of Pathology and Internal Medicine, University of Pennyslvania School of Medicine, Philadelphia, PA, USA
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Publication History

Publication Date:
09 July 2018 (online)

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  • References

  • 1 Wright JH. The origin and nature of blood platelets. Boston Med Surg J 1906; 154: 643
    CrossrefPubMedGoogle Scholar
  • 2 Haiker LA. Megakaryocyte quantitation. J Clin Invest 1968; 47: 452
    CrossrefPubMedGoogle Scholar
  • 3 Stenberg PE, Levin J. Mechanisms of platelet production. Blood Cells 1989; 15: 23-47
    PubMedGoogle Scholar
  • 4 Corash L, Levin J, Mok Y, Baker G, McDowell J. Measurement of megakaryocyte frequency and ploidy distribution in unfractionated murine bone marrow. Exp Hematol 1989; 17: 278
    PubMedGoogle Scholar
  • 5 Tavassoli M, Add M. Localization of megakaryocytes in the bone marrow. Blood Cells 1989; 15: 3
    PubMedGoogle Scholar
  • 6 Pedersen NT. The pulmonary vessels as a filter for circulating megakaryocytes. Scand J Haematol 1974; 13: 225
    PubMedGoogle Scholar
  • 7 Vainchenker W, Bouget J, Guichard J, Breton-Gorius J. Megakaryocyte colony formation from human bone marrow precursors. Blood 1979; 54: 940
    PubMedGoogle Scholar
  • 8 Gewirtz AM. Recent methodologic advances in the study of human megakaryocyte development and function. In: Pharmacologic Methods for the Investigation of Coagulation and Platelets. Colman RW, Smith BJ. eds. Alan R. Liss; New York: 1987: 1-18
    Google Scholar
  • 9 Gewirtz AM. Use of in situ hybridization to study human megakaryocyte gene expression. Prog Clin Biol Res 1990; 356: 105-117
    PubMedGoogle Scholar
  • 10 Choi E, Nichol JL, Hokom MM, Homkohl AC, Hunt P. Platelets generated in vitro from proplatelet-displaying human megakaryocytes are functional. Blood 1995; 85: 402-413
    PubMedGoogle Scholar
  • 11 Metcalf D. Thrombopoietin - at last. Nature 1994; 369: 519
    CrossrefPubMedGoogle Scholar
  • 12 Briddell RA, Hoffman R. Cytokine regulation of the human burstforming unit-megakaryocyte. Blood 1990; 76: 516-522
    PubMedGoogle Scholar
  • 13 Briddell RA, Brandt JE, Straneva JE, Srour EF, Hoffman R. Characterization of the human burst-forming unit-megakaryocyte. Blood 1989; 74: 145-151
    PubMedGoogle Scholar
  • 14 Long MW, Heffner CH, Gragowski LL. In vitro differences in responsiveness of early (BFU-Mk) and late (CFU-Mk) murine megakaryocyte progenitor cells. Prog.Qin.Biol.Res 1986; 215: 179-186
    PubMedGoogle Scholar
  • 15 Long MW, Gragowski LL, Heffner CH, Boxer LA. Phorbol diesters stimulate the development of an early murine progenitor cell: The burst forming unit-megakaryocyte (BFU-Mk). J Clin Invest 1985; 76: 431-438
    CrossrefPubMedGoogle Scholar
  • 16 Mazur EM, Hoffman R, Bruno E, Chasis J, Marchesi S. Immunofluorescent identification of human megakaryocyte colonies using an antiplatelet glycoprotein antiserum. Blood 1981; 57: 277-286
    PubMedGoogle Scholar
  • 17 Vainchenker W, Bouget J, Guichard J, Breton-Gorius J. Megakaryocyte colony formation from human bone marrow precursors. Blood 1979; 54: 940-945
    PubMedGoogle Scholar
  • 18 Metcalf D, MacDonald HR, Odartchenko N, Sordat B. Growth of mouse megakaryocyte colonies in vitro. Proc Natl Acad Sci USA 1975; 72: 1744-1748
    CrossrefPubMedGoogle Scholar
  • 19 Nakeff A, Daniels-McQueen S. In vitro colony assay for a new class of megakaryocyte precursor. Colony-forming unit megakaryocyte precursor: Colony forming unit megakaryocyte (CFU-M) Proc Soc Exp Biol Med 1976; 151: 587-590
    CrossrefPubMedGoogle Scholar
  • 20 Chatelain C, De Bast M, Symann M. Identification of a light density murine megakaryocyte progenitor (LD-CFU-M). Blood 1988; 72: 1187-1192
    PubMedGoogle Scholar
  • 21 Long MW, Williams N. Immature megakaryocytes in mouse: Morphology and quantitation by acetylcholinesterase staining. Blood 1981; 58: 1032-1039
    PubMedGoogle Scholar
  • 22 Gewirtz AM, Hoffman R. Transitory hypomegakaryocytic thrombocytopenic purpura: Etiologic association with ethanol abuse and implications regarding regulation of human magakaryocytopoiesis. Br J Haematol 1986; 62: 333-344
    CrossrefPubMedGoogle Scholar
  • 23 Long MW, Williams N, McDonald TP. Immature megakaryocytes in the mouse: In vitro relationship to megakaryocyte progenitor cells and mature megakaryocytes. J Cell Physiol 1982; 112: 339-344
    CrossrefPubMedGoogle Scholar
  • 24 Zucker-Franklin D. Megakaryocytes and platelets. In: Atlas of Blood Cells Function and Pathology. Zucker-Franklin D, Greaves MF, Grossi CE, Marmont AM. eds. Lea and Febiger; Philadelphia, PA: 1988: 621-693
    Google Scholar
  • 25 Williams N, Eger RR, Jackson HM, Nelson DJ. Twofactorrequirements formurine megakaryocyte colony formation. J Cell Physiol 1982; 110: 101-104
    CrossrefPubMedGoogle Scholar
  • 26 Hoffman R, Mazur E, Bruno E, Floyd V. Assay of an activity in the serum of patients with disorders of thrombopoiesis that stimulates formation of megakaryocytic colonies. N Engl J Med 1975; 305: 533-538
    PubMedGoogle Scholar
  • 27 McDonald TP, Andrews RB, Clift R, Cottrell M. Characterization of a thrombocytopoietic stimulating factor from kidney cell culture medium. Exp Hematol 1981; 9: 288-296
    PubMedGoogle Scholar
  • 28 Levin J, Levin FC, Hull III DF, Penington DG. The effects of thrombopoietin on megakaryocyte-CFU, megakaryocytes and thrombopoiesis: With studies of ploidy an platelet size. Blood 1982; 60: 989-998
    PubMedGoogle Scholar
  • 29 de Sauvage FJ, Hass PE, Spencer SD, Malloy BE, Gurney AL, Spencer SA, Darbonne WC, Henzel WJ, Wong SC, Kuang WJ, Oles KJ, Hultgren B, Solberg LA, Goeddel DV, Eaton DL. Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-mpl lig . Nature 1994; 369: 533-538
    CrossrefPubMedGoogle Scholar
  • 30 Lok S, Kaushansky K, Holly RD, Kuijper JL, Lofton-Day CE, Oort PJ, Grant FJ, Keipel MD, Burkhead SK, Kramer JM, Bell LA, Sprecher CA, Blumberg H, Johnson R, Prunkard D, Ching AF T, Mathewes SL, 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: 565-568
    CrossrefPubMedGoogle Scholar
  • 31 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: 568-571
    CrossrefPubMedGoogle Scholar
  • 32 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; 639: 571-574
    PubMedGoogle Scholar
  • 33 Souyri M, Vignon I, Penciolelli JK, Heard JM, Tambourin P, Wendling F. A putative truncated cytokine receptor gene tranduced by the myeloproliferative leukemia vims immmortalizes hematopoietic progenitors. Cell 1990; 63: 1137-1147
    CrossrefPubMedGoogle Scholar
  • 34 Methia N, Louache F, Vainchenker W, Wendling F. Oligonucleotides antisense to the protooncogene c-mpl specifically inhibit in vitro megakaryocytopoiesis. Blood 1993; 82: 1395-1401
    PubMedGoogle Scholar
  • 35 Gewirtz AM, Calabretta B. A c-myb antisense oligodeoxynucleotide inhibits normal human hematopoiesis in vitro. Science 1988; 245: 1303-1306
    PubMedGoogle Scholar
  • 36 Gumey AL, Carver-Moore K, de Sauvage FJ, Moore MW. Thrombocytopenia in c-mpl-deficient mice. Science 1994; 265: 1445-1447
    CrossrefPubMedGoogle Scholar
  • 37 Vignon I, Florindo C, Fichelson S, Guenet JL, Mattei MG, Souyri M, Cosman D, Gisslebrecht S. Characterization of the murine mpl protooncogene, a member of the hematopoietic cytokine recptorfamily: Molecular cloning, chromosomal location, and evidence for a function in cell growth. Oncogene 1993; 8: 2607-2615
    PubMedGoogle Scholar
  • 38 Foster DC, Sprecher CA, Grant FJ, Kramer JM, Kuijper JL, Holly Rd, Whitmore TE, Heipel MK, Bell A, Ching AF T, McGrane V, Hart C, O’Hara PJ, Lok S. Human thrombopoietin: Gene structure, cDNA sequence, expression, and chromosomal localization. Proc Natl Acad Sci USA 1994; 91: 13023-13027
    CrossrefPubMedGoogle Scholar
  • 39 Gumey AL, Kuang WJ, Xie MH, Malloy BE, Eaton DL, de Sauvage FJ. Genomic structure, chromosomal localization, and conserved alternative splice forms of thrombopoietin. Blood 1995; 85: 981-988
    PubMedGoogle Scholar
  • 40 Messner HA, Jamal N, Izaguirre C. The growth oflarge megakaryocyte colonies from human bone marrow. J. Cell Physiol 1982; (Suppl) l: 45-51
    PubMedGoogle Scholar
  • 41 Vainchenker W, Chapman J, Deschamps JF, Vinci G, Bouget J, Titeux M, Breton-Gorius J. Normal human serum contains a factors) capable of inhibiting megakaryocyte colony formation. Exp Hematol 1982; 10: 650
    PubMedGoogle Scholar
  • 42 Solberg Jr LA, Jamal N, Messner HA. Characterization of human megakaryocytic colony formation in human plasma. J Cell Physiol 1985; 124: 67
    CrossrefPubMedGoogle Scholar
  • 43 Dessypris EN, Gleaton JH, Sawyer ST, Armstrong OL. Suppression of maturation of megakaryocyte colony forming unit in vitro by a platelet released glycoprotein. J Cell Physiol 1987; 130: 361
    CrossrefPubMedGoogle Scholar
  • 44 Mitjavila MT, Vinci G, Villeval JL, Kieffer N, Henri A, Testa U, Breton-Gorius J, Vainchenker W. Human platelet alpha granules contain a nonspecific inhibitor of megakaryocyte colony formation: its relationship to type beta transforming growth factor (TGF-beta). J Cell Physiol 1988; 134: 93-100
    CrossrefPubMedGoogle Scholar
  • 45 Ishibashi T, Miller SL, Burstein SA. Type-B transforming growth factor is a potent inhibitor of murine megakaryocytopoiesis in vitro. Blood 1987; 69: 1737-1741
    PubMedGoogle Scholar
  • 46 Han ZC, Bellucci S, Walz A, Baggiolini M, Caen JP. Negative regulation of human megakaryocytopoiesis by human platelet factor 4 (PF4) and connective tissue-activating peptide (CTAP-III). Int. J. Cell Cloning 1990; 8: 253-259
    CrossrefPubMedGoogle Scholar
  • 47 Han ZC, Sensebe L, Abgrall JF, Briere J. Platelet factor 4 inhibits human megakaryocytopoiesis in vitro. Blood 1990; 75: 1234-1239
    PubMedGoogle Scholar
  • 48 Gewirtz AM, Calabretta B, Rucinski B, Niewiarowski S, Xu WY. Inhibition of human megakaryocytopoiesis in vitro by platelet factor 4 (PF4) and a synthetic COOH-terminal PF4 peptide. J Clin Invest 1989; 83: 1477-1486
    CrossrefPubMedGoogle Scholar
  • 49 Baggiolini M, Dewald B, Moser B. Interleukin-8 and related chemotactic cytokines-CXC and CC chemokines. Adv Immunol 1994; 55: 97
    PubMedGoogle Scholar
  • 50 Gewirtz AM, Zhang J, Ratajczak J, Ratajczak M, Park K S, Li C, Yan Z, Poncz M. Chemokine Regulation of Human Megakaryocytopoiesis (submitted for publication).
    PubMedGoogle Scholar
  • 51 Lifson-Lapidot Y, Patinkin D, Prody CA, Ehrlich G, Seidman S, Ben-Aziz R, Benseler F, Exkstien F, Zakut H, Soreq H. Cloning and anitsense oligodeoxynucleotide inhibition of a human homolog of cdc2 required in hematopoiesis. Proc Natl Acad Sci USA 1992; 89: 579-583
    CrossrefPubMedGoogle Scholar
  • 52 White JG. Mechanisms of platelet production. Blood Cells 1989; 15: 48-57
    PubMedGoogle Scholar
  • 53 Choi ES, Nichol JL, Hokom MM, Homkohl AC, Hunt P. Platelets generated in vitro from pro-platelet displaying human megakaryocytes are functional. Blood 1995; 85: 402-413
    PubMedGoogle Scholar
  • 54 Xiong T, Kuczynski WI, Gewirtz AM. Strategies for detecting developmentally regulated genes in normal human megakaryocytes. Blood 1994; 84 (01) 322a-322a
    PubMedGoogle Scholar
  • 55 Mazur EM, Cohen JL, Newton J, Sohl P, Narendran A, Gesner TG, Mafuson RA. Human serum megakaryocyte colony-stimulating activity appears to be distinct from interleukin-3, granulocyte-macrophage colony- stimulating factor, and lymphocyte-conditioned medium. Blood 1990; 76: 290-297
    PubMedGoogle Scholar
  • 56 Dessypris EN, Chuncharunee S, Frieson KE. Thrombopoiesis - stimulating factor: its effects on megakaryocyte colony formation in vitro and its relation to human granulocyte-macrophage colony-stimulating factor. Exp Hematol 1990; 18: 754-757
    PubMedGoogle Scholar
  • 57 Emerson SG, Yang YC, Clark SC, Long MW. Human recombinant granulocyte-macrophage colony stimulating factor and inteleukin-3 have overlapping but distinct hematopoietic activities. I din Invest 1988; 82: 1282-1287
    PubMedGoogle Scholar
  • 58 Ishibashi T, Kimura H, Shikama Y, Uchida T, Kariyone S, Maruyama Y. Effect of recombinant granulocyte -macrophage colony-stimulating factor on murine thrombocytopoiesis in vitro and in vivo. Blood 1990; 75: 1433-1438
    PubMedGoogle Scholar
  • 59 Ishida Y, Yano S, Yoshida T, Tanaka H, Yamada Y, Kawano M, Kaneko T, Matsumoto N. Biological effects of recombinant erythropoietin, granulocyte-macrophage colony-stimulating factor, interleukin-3, and interleukin-6 on purified rat megakaryocytes. Exp Hematol 1991; 19: 608-612
    PubMedGoogle Scholar
  • 60 Maruyama T, Kobayashi F, Uchida K, Hara H. Effect of antibiotics on colony formation from mouse granulocyte-macrophage progenitors (CFU- GM), megakaryocyte progenitors (CFU-M) and erythrocyte progenitors (CFU-E, BFU-E) in vitro. Pharmacol Toxicol 1989; 64: 391-396
    CrossrefPubMedGoogle Scholar
  • 61 Schuening FG, Storb R, Gochle S, Nash R, Graham TC, Appelbaum FR, Hackman R, Sandmaier B M, Urdal DL. Stimulation of canine hematopoiesis by recombinant human granulocyte-macrophage colony- stimulating factor. Exp Hematol 1989; 17: 889-894
    PubMedGoogle Scholar
  • 62 Bruno E, Briddell R, Hoffman R. Effect of recombinant purified hematopoietic growth factor cm human megakaryocyte colony formation. Exp Hematol 1988; 16: 371-377
    PubMedGoogle Scholar
  • 63 Bmno E, Cooper RJ, Briddell R, Hoffman R. Further examination of the effects of recombinant cytokines on the proliferation of human megakaryocyte progenitor cells. Blood 1991; 77: 2339-2346
    PubMedGoogle Scholar
  • 64 Bmno E, Miller ME, Hoffman R. Interacting cytokines regulate in vitro human megakaryocytopoiesis. Blood 1989; 73: 671-677
    PubMedGoogle Scholar
  • 65 Quesenberry PJ, McGrath HE, McNiece IK, Temeles DS, Robinson BE. Growth factor stimulation of murine megakaryocyte colony formation. Prog Clin Biol Res 1990; 356: 155-165
    PubMedGoogle Scholar
  • 66 Robinson BE, McGrath HE, Quesenberry PJ. Recombinant murine granulocyte macrophage colony-stimulating factor has megakaryocyte colony-stimulating activity and augments megakaryocyte colony stimulation by interleukin-3. J Clin Invest 1987; 79: 1648-1652
    CrossrefPubMedGoogle Scholar
  • 67 Geissler K, Valent P, Bettelheim P, Sillaber C, Wagner B, Kyrle P, Hinterberger W, Lechner K, Liehl E, Mayer P. In vivo synergism of recombinant human interleukin-3 and recombinant human interleukin-6 cm thrombopoiesis in primates. Blood 1992; 79: 1155-1160
    PubMedGoogle Scholar
  • 68 Mazur EM, Cohen JL, Bogart L, Mufson RA, Gesner TG, Yang YC, Clark SC. Recombinant gibbon interleukin-3 stimulates megakaryocyte colony growth in vitro from human peripheral blood progenitor cells. J Cell Physiol 1988; 136: 439-446
    CrossrefPubMedGoogle Scholar
  • 69 McNiece IK, McGrath HE, Quesenberry PJ. Granulocyte colony- stimulating factor augments in vitro megakaryocyte colony formation by interleukin-3. Exp Hematol 1988; 16: 807-810
    PubMedGoogle Scholar
  • 70 Segal GM, Stueve T, Adamson JW. Analysi s of murine megakaryocyte colony size and ploidy: effects of interleukin-3. J Cell Physiol 1988; 137: 537-544
    CrossrefPubMedGoogle Scholar
  • 71 Suda J, Suda T, Kubota K, Ihle J N, Saito M, Miura Y. Purified interleukin-3 and erythropoietin support the terminal differentiation of hemotopoietic progenitors in seum-free culture. Blood 1986; 67: 1002
    PubMedGoogle Scholar
  • 72 Messner HA, Yamasaki K, Jamal N, Minden MM, Yang YC, Wong GC, Clark SC. Growth of human hematopoietic colonies in response to recombinant gibbon interleukin-3. Comparison with recombinant granulocyte and granulocyte-macrophage colony stimulating factor. Proc Natl Acad Sci USA 1987; 84: 6765
    CrossrefPubMedGoogle Scholar
  • 73 Bruno E, Miller ME, Hoffman R. Interacting cytokines regulate in vitro human megakaryocytopoiesis. Blood 1989; 76: 671
    PubMedGoogle Scholar
  • 74 Koike K, Nakahata T, Kubo T, Kikuchi T, Takagi M, Ishiguro A, Tsuji K, Naganuma K, Okano A, Akiyama Y. Inteleukin-6 enhances murine megakaryocytopoiesis in serum-free culture. Blood 1990; 75: 2286-2291
    PubMedGoogle Scholar
  • 75 Lotem J, Shabo Y, Sachs L. Regulation of megakaryocyte development by interleukin-6. Blood 1989; 74: 1545-1551
    PubMedGoogle Scholar
  • 76 Rennick D, Jackson J, Yang G, Wideman J, Lee F, Hudak S. Interleukin- 6 interacts with interleukin-4 and other hematopoietic growth factors to selectively enhance the growth of megakaryocytic, erythroid, myeloid, and multipotential progenitor cells. Blood 1989; 73: 1828-1835
    PubMedGoogle Scholar
  • 77 Leven RM, Rodriguez A. Immunomagnetic bead isolation of megakaryocytes from guinea-pig bone marrow: effect of recombinant interleukin-6 on size, ploidy and cytoplasmic fragmentation. Br J Haematol 1991; 77: 267-273
    CrossrefPubMedGoogle Scholar
  • 78 Imai T, Koike K, Kikuchi T, Amano Y, Takagi M, Okumura N, Nakahata T. Interleukin-6 supports human megakaryocytic proliferation and differentiation m vitro. Blood 1991; 78: 1969-1974
    PubMedGoogle Scholar
  • 79 Navarro S, Debili N, Le Couedic JP, Klein B, Breton-Gorius J, Doly J, Vaichenker W. Interleukin-6 and its receptors are expressed by human megakaryocytes: in vitro effects on proliferation and endoreplication. Blood 1991; 77: 461-471
    PubMedGoogle Scholar
  • 80 Avraham H, Vannier E, Cowley S, Jiang SX, 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
    PubMedGoogle Scholar
  • 81 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
    PubMedGoogle Scholar
  • 82 Carow CE, Hangoc G, Cooper SH, Williams DE, Broxmeyer HE. Mast cell growth factor (c-kit ligand) supports the growth ofhuman multipotential progenitor cells with a high replating potential. Blood 1991; 78: 2216-2221
    PubMedGoogle Scholar
  • 83 Fraser JK, Lin FK, Berridge MV. Expression og high affinity receptors for erythropoietin on human bone marrow cells and on the human erythroleukemic cell line, HEL. Exp Hematol 1988; 16: 836-842
    PubMedGoogle Scholar
  • 84 Paul SR, Bennett F, Calvetti JA, Kelleher K, Wood CR, O’Hara Jr RM, Leary AC, Sibley B, Clark SC, Williams DA. Molecular cloning of a cDNA encoding interleukin-11, a stromal cell-derived lymphopoietic and hematopoietic cytokine. Proc Natl Acad Sci USA 1990; 87: 7512-7516
    CrossrefPubMedGoogle Scholar
  • 85 Bruno E, Briddell RA, Cooper RJ, Hoffman R. Effects of recombinant interleukin-11 on human megakaryocyte progenitor cells. Exp Hematol 1991; 19: 378-381
    PubMedGoogle Scholar
  • 86 Teramura M, Kobayashi S, Hoshino S, Oshimi K, Mizoguchi H. Interleukin-11 enhances human megakaryocytopoiesis in vitro. Blood 1992; 79: 327-331
    PubMedGoogle Scholar