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. 1995 Jun;95(6):2973–2978. doi: 10.1172/JCI118005

Megakaryocyte growth and development factor. Analyses of in vitro effects on human megakaryopoiesis and endogenous serum levels during chemotherapy-induced thrombocytopenia.

J L Nichol 1, M M Hokom 1, A Hornkohl 1, W P Sheridan 1, H Ohashi 1, T Kato 1, Y S Li 1, T D Bartley 1, E Choi 1, J Bogenberger 1, et al.
PMCID: PMC295986  PMID: 7539462

Abstract

The present study shows that recombinant human megakaryocyte growth and development factor (r-HuMGDF) behaves both as a megakaryocyte colony stimulating factor and as a differentiation factor in human progenitor cell cultures. Megakaryocyte colony formation induced with r-HuMGDF is synergistically affected by stem cell factor but not by interleukin 3. Megakaryocytes stimulated with r-HuMGDF demonstrate progressive cytoplasmic and nuclear maturation. Measurable levels of megakaryocyte growth and development factor in serum from patients undergoing myeloablative therapy and transplantation are shown to be elaborated in response to thrombocytopenic stress. These data support the concept that megakaryocyte growth and development factor is a physiologically regulated cytokine that is capable of supporting several aspects of megakaryopoiesis.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arriaga M., South K., Cohen J. L., Mazur E. M. Interrelationship between mitosis and endomitosis in cultures of human megakaryocyte progenitor cells. Blood. 1987 Feb;69(2):486–492. [PubMed] [Google Scholar]
  2. Bartley T. D., Bogenberger J., Hunt P., Li Y. S., Lu H. S., Martin F., Chang M. S., Samal B., Nichol J. L., Swift S. Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor Mpl. Cell. 1994 Jul 1;77(7):1117–1124. doi: 10.1016/0092-8674(94)90450-2. [DOI] [PubMed] [Google Scholar]
  3. Bruno E., Miller M. E., Hoffman R. Interacting cytokines regulate in vitro human megakaryocytopoiesis. Blood. 1989 Feb 15;73(3):671–677. [PubMed] [Google Scholar]
  4. Debili N., Hegyi E., Navarro S., Katz A., Mouthon M. A., Breton-Gorius J., Vainchenker W. In vitro effects of hematopoietic growth factors on the proliferation, endoreplication, and maturation of human megakaryocytes. Blood. 1991 Jun 1;77(11):2326–2338. [PubMed] [Google Scholar]
  5. Fukunaga R., Ishizaka-Ikeda E., Nagata S. Growth and differentiation signals mediated by different regions in the cytoplasmic domain of granulocyte colony-stimulating factor receptor. Cell. 1993 Sep 24;74(6):1079–1087. doi: 10.1016/0092-8674(93)90729-a. [DOI] [PubMed] [Google Scholar]
  6. Hegyi E., Nakazawa M., Debili N., Navarro S., Katz A., Breton-Gorius J., Vainchenker W. Developmental changes in human megakaryocyte ploidy. Exp Hematol. 1991 Feb;19(2):87–94. [PubMed] [Google Scholar]
  7. Hill R. J., Leven R. M., Levin F. C., Levin J. The effect of partially purified thrombopoietin on guinea pig megakaryocyte ploidy in vitro. Exp Hematol. 1989 Sep;17(8):903–907. [PubMed] [Google Scholar]
  8. Hill R. J., Levin J., Levin F. C. Correlation of in vitro and in vivo biological activities during the partial purification of thrombopoietin. Exp Hematol. 1992 Mar;20(3):354–360. [PubMed] [Google Scholar]
  9. Hill R., Levin J. Partial purification of thrombopoietin using lectin chromatography. Exp Hematol. 1986 Sep;14(8):752–759. [PubMed] [Google Scholar]
  10. Hoffman R., Yang H. H., Bruno E., Straneva J. E. Purification and partial characterization of a megakaryocyte colony-stimulating factor from human plasma. J Clin Invest. 1985 Apr;75(4):1174–1182. doi: 10.1172/JCI111813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kuramochi S., Chiba T., Amanuma H., Tojo A., Todokoro K. Growth signal erythropoietin activates the same tyrosine kinases as interleukin 3, but activates only one tyrosine kinase as differentiation signal. Biochem Biophys Res Commun. 1991 Dec 31;181(3):1103–1109. doi: 10.1016/0006-291x(91)92052-l. [DOI] [PubMed] [Google Scholar]
  12. Kuter D. J., Beeler D. L., Rosenberg R. D. The purification of megapoietin: a physiological regulator of megakaryocyte growth and platelet production. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11104–11108. doi: 10.1073/pnas.91.23.11104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Levine R. F., Hazzard K. C., Lamberg J. D. The significance of megakaryocyte size. Blood. 1982 Nov;60(5):1122–1131. [PubMed] [Google Scholar]
  14. Lok S., Kaushansky K., Holly R. D., Kuijper J. L., Lofton-Day C. E., Oort P. J., Grant F. J., Heipel M. D., Burkhead S. K., Kramer J. M. Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo. Nature. 1994 Jun 16;369(6481):565–568. doi: 10.1038/369565a0. [DOI] [PubMed] [Google Scholar]
  15. Long M. W., Williams N. Immature Megakaryocytes in the Mouse: Morphology and quantitation by acetylcholinesterase staining. Blood. 1981 Nov;58(5):1032–1039. [PubMed] [Google Scholar]
  16. Martin F. H., Suggs S. V., Langley K. E., Lu H. S., Ting J., Okino K. H., Morris C. F., McNiece I. K., Jacobsen F. W., Mendiaz E. A. Primary structure and functional expression of rat and human stem cell factor DNAs. Cell. 1990 Oct 5;63(1):203–211. doi: 10.1016/0092-8674(90)90301-t. [DOI] [PubMed] [Google Scholar]
  17. Mazur E. M., Basilico D., Newton J. L., Cohen J. L., Charland C., Sohl P. A., Narendran A. Isolation of large numbers of enriched human megakaryocytes from liquid cultures of normal peripheral blood progenitor cells. Blood. 1990 Nov 1;76(9):1771–1782. [PubMed] [Google Scholar]
  18. Mazur E. M., Hoffman R., Chasis J., Marchesi S., Bruno E. Immunofluorescent identification of human megakaryocyte colonies using an antiplatelet glycoprotein antiserum. Blood. 1981 Feb;57(2):277–286. [PubMed] [Google Scholar]
  19. Mazur E. M., South K. Human megakaryocyte colony-stimulating factor in sera from aplastic dogs: partial purification, characterization, and determination of hematopoietic cell lineage specificity. Exp Hematol. 1985 Dec;13(11):1164–1172. [PubMed] [Google Scholar]
  20. Mazur E. M., de Alarcón P., South K., Miceli L. Human serum megakaryocyte colony-stimulating activity increases in response to intensive cytotoxic chemotherapy. Exp Hematol. 1984 Sep;12(8):624–628. [PubMed] [Google Scholar]
  21. McDonald T. P., Clift R., Lange R. D., Nolan C., Tribby I. I., Barlow G. H. Thrombopoietin production by human embryonic kidney cells in culture. J Lab Clin Med. 1975 Jan;85(1):59–66. [PubMed] [Google Scholar]
  22. McDonald T. P. Thrombopoietin: its biology, purification, and characterization. Exp Hematol. 1988 Mar;16(3):201–205. [PubMed] [Google Scholar]
  23. McLeod D. L., Shreve M. M., Axelrad A. A. Induction of megakaryocyte colonies with platelet formation in vitro. Nature. 1976 Jun 10;261(5560):492–494. doi: 10.1038/261492a0. [DOI] [PubMed] [Google Scholar]
  24. McNiece I. K., Langley K. E., Zsebo K. M. Recombinant human stem cell factor synergises with GM-CSF, G-CSF, IL-3 and epo to stimulate human progenitor cells of the myeloid and erythroid lineages. Exp Hematol. 1991 Mar;19(3):226–231. [PubMed] [Google Scholar]
  25. Metcalf D. The molecular control of cell division, differentiation commitment and maturation in haemopoietic cells. Nature. 1989 May 4;339(6219):27–30. doi: 10.1038/339027a0. [DOI] [PubMed] [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 Sep 1;82(5):1395–1401. [PubMed] [Google Scholar]
  27. Nichol J. L., Hornkohl A. C., Choi E. S., Hokom M. M., Ponting I., Schuening F. W., Hunt P. Enrichment and characterization of peripheral blood-derived megakaryocyte progenitors that mature in short-term liquid culture. Stem Cells. 1994 Sep;12(5):494–505. doi: 10.1002/stem.5530120505. [DOI] [PubMed] [Google Scholar]
  28. ODELL T. T., Jr, McDONALD T. P., DETWILER T. C. Stimulation of platelet production by serum of platelet-depleted rats. Proc Soc Exp Biol Med. 1961 Nov;108:428–431. doi: 10.3181/00379727-108-26958. [DOI] [PubMed] [Google Scholar]
  29. Ogata K., Zhang Z. G., Abe K., Murphy M. J., Jr Partial purification and characterization of human megakaryocyte colony-stimulating factor (Meg-CSF). Int J Cell Cloning. 1990 Jan;8 (Suppl 1):103–120. doi: 10.1002/stem.5530080710. [DOI] [PubMed] [Google Scholar]
  30. Sheridan W. P., Begley C. G., Juttner C. A., Szer J., To L. B., Maher D., McGrath K. M., Morstyn G., Fox R. M. Effect of peripheral-blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy. Lancet. 1992 Mar 14;339(8794):640–644. doi: 10.1016/0140-6736(92)90795-5. [DOI] [PubMed] [Google Scholar]
  31. Sheridan W. P., Begley C. G., To L. B., Grigg A., Szer J., Maher D., Green M. D., Rowlings P. A., McGrath K. M., Cebon J. Phase II study of autologous filgrastim (G-CSF)-mobilized peripheral blood progenitor cells to restore hemopoiesis after high-dose chemotherapy for lymphoid malignancies. Bone Marrow Transplant. 1994 Jul;14(1):105–111. [PubMed] [Google Scholar]
  32. Straneva J. E., Goheen M. P., Hui S. L., Bruno E., Hoffman R. Terminal cytoplasmic maturation of human megakaryocytes in vitro. Exp Hematol. 1986 Nov;14(10):919–929. [PubMed] [Google Scholar]
  33. Vainchenker W., Bouguet J., Guichard J., Breton-Gorius J. Megakaryocyte colony formation from human bone marrow precursors. Blood. 1979 Oct;54(4):940–945. [PubMed] [Google Scholar]
  34. Vainchenker W., Guichard J., Breton-Gorius J. Growth of human megakaryocyte colonies in culture from fetal, neonatal, and adult peripheral blood cells: ultrastructural analysis. Blood Cells. 1979 Mar 23;5(1):25–42. [PubMed] [Google Scholar]
  35. Vigon I., Florindo C., Fichelson S., Guenet J. L., Mattei M. G., Souyri M., Cosman D., Gisselbrecht S. Characterization of the murine Mpl proto-oncogene, a member of the hematopoietic cytokine receptor family: molecular cloning, chromosomal location and evidence for a function in cell growth. Oncogene. 1993 Oct;8(10):2607–2615. [PubMed] [Google Scholar]
  36. Wendling F., Maraskovsky E., Debili N., Florindo C., Teepe M., Titeux M., Methia N., Breton-Gorius J., Cosman D., Vainchenker W. cMpl ligand is a humoral regulator of megakaryocytopoiesis. Nature. 1994 Jun 16;369(6481):571–574. doi: 10.1038/369571a0. [DOI] [PubMed] [Google Scholar]
  37. de Sauvage F. J., Hass P. E., Spencer S. D., Malloy B. E., Gurney A. L., Spencer S. A., Darbonne W. C., Henzel W. J., Wong S. C., Kuang W. J. Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand. Nature. 1994 Jun 16;369(6481):533–538. doi: 10.1038/369533a0. [DOI] [PubMed] [Google Scholar]

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