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Biology of Thrombopoietin In the Human Foetus and Neonate

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Neonatology and Blood Transfusion

Part of the book series: Developments in Hematology and Immunology ((DIHI,volume 39))

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Abstract

The aim of this contribution is to summarize the current data on the biology of thrombopoietin (Tpo) in the human foetus and neonate.

Authors’ work is supported by the Deutsche Forschungsgemeinschaft (DA 484/2-1).

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References

  1. de Sauvage FJ, Hass PE, Spencer SD, et al. Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand. Nature 1994;369:533–538.

    PubMed  Google Scholar 

  2. Lok S, Kaushansky K, Holly RD, et al. Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo. Nature 1994;369:565–568.

    CAS  PubMed  Google Scholar 

  3. Kaushansky K, Lok S, Holly RD, et al. Promotion of megakaryocyte progenitor expansion and differentiation by the c-Mpl ligand thrombopoietin. Nature 1994;369:568–571.

    CAS  PubMed  Google Scholar 

  4. Wendling F, Maraskovsky E, Debili N, et al. cMpl ligand is a humoral regulator of megakaryocytopoiesis. Nature 1994;369:571–574.

    CAS  PubMed  Google Scholar 

  5. Bartley TD, Bogenberger J, Hunt P, et al. Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor Mpl. Cell 1994;77:1117–1124.

    CAS  PubMed  Google Scholar 

  6. Sohma Y, Akahori H, Seki N, et al. Molecular cloning and chromosomal localization of the human thrombopoietin gene. FEBS Lett 1994;353:57–61.

    CAS  PubMed  Google Scholar 

  7. Kelemen E, Cserhati I, Tanos B. Demonstration and some properties of human thrombopoietin in thrombocythaemic sera. Acta Haematologica Basel 1958;20:350–355.

    CAS  Google Scholar 

  8. Vigon I, Mornon JP, Cocault L, et al. 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;89:5640–5644.

    CAS  PubMed  Google Scholar 

  9. de Sauvage FJ, Carver-Moore K, Luoh SM, et al. Physiological regulation of early and late stages of megakaryocytopoiesis by thrombopoietin. J Exp Med 1996;183:651–656.

    PubMed  Google Scholar 

  10. Choi ES, Hokom M, Bartley T, et al. Recombinant human megakaryocyte growth and development factor (rHuMGDF), a ligand for c-Mpl, produces functional human platelets in vitro. Stem Cells 1995;13:317–322.

    CAS  PubMed  Google Scholar 

  11. Gurney AL, Carver-Moore K, de Sauvage FJ, Moore MW. Thrombocytopenia in c-mpl deficient mice. Science 1994;265:1445–1447.

    CAS  PubMed  Google Scholar 

  12. Kaushansky K. Thrombopoietin: the primary regulator of platelet production. Blood 1995;86:419–431.

    CAS  PubMed  Google Scholar 

  13. Debili N, Masse JM, Katz A, Guichard J, Breton-Gorius J, Vainchenker W. Effects of the recombinant hematopoietic growth factors interleukin-3, interleukin-6, stem cell factor, and leukemia inhibitory factor on the megakaryocytic differentiation of CD34+ cells. Blood 1993;82:84–95.

    CAS  PubMed  Google Scholar 

  14. Yang M, Li K, Chui CM, Yuen PM, et al. Expression of interleukin (IL) 1 type I and type II receptors in megakaryocytic cells and enhancing effects of IL-1beta on megakaryocytopoiesis and NF-E2 expression. Br J Haematol 2000;111:371–380.

    CAS  PubMed  Google Scholar 

  15. Scott CL, Robb L, Mansfield R, Alexander WS, Begley CG. Granulocytemacrophage colony-stimulating factor is not responsible for residual thrombopoiesis in mpl null mice. Exp Hematol 2000;28:1001–1007.

    CAS  PubMed  Google Scholar 

  16. Gainsford T, Roberts AW, Kimura S, et al. Cytokine production and function in c-mpl-deficient mice: no physiologic role for interleukin-3 in residual megakaryocyte and platelet production. Blood 1998;91:2745–2752.

    CAS  PubMed  Google Scholar 

  17. Gainsford T, Nandurkar H, Metcalf D, Robb L, Begley CG, Alexander WS. The residual megakaryocyte and platelet production in c-mpl-deficient mice is not dependent on the actions of interleukin-6, interleukin-11, or leukemia inhibitory factor. Blood 2000;95:528–534.

    CAS  PubMed  Google Scholar 

  18. Sola MC, Du Y, Hutson AD, Christensen RD. Dose-response relationship of megakaryocyte progenitors from the bone marrow of thrombocytopenic and non-thrombocytopenic neonates to recombinant thrombopoietin. Br J Haematol 2000;110:449–453.

    CAS  PubMed  Google Scholar 

  19. Eisbacher M, Khachigian LM, Khin TH, Holmes ML, Chong BH. Inducible expression of the megakaryocyte-specific gene glycoprotein IX is mediated through an Ets binding site and involves upstream activation of extracellular signal-regulated kinase. Cell Growth Differ 2001;12:435–445.

    CAS  PubMed  Google Scholar 

  20. Doubeikovski A, Uzan G, Doubeikovski Z, et al. Thrombopoietin-induced expression of the glycoprotein IIb gene involves the transcription factor PU.1/Spi-1 in UT7-Mpl cells. J Biol Chem 1997;272:24300–24307.

    CAS  PubMed  Google Scholar 

  21. Holmes ML, Bartle N, Eisbacher M, Chong BH. Cloning and analysis of the thrombopoietin-induced megakaryocyte-specific glycoprotein VI promoter and its regulation by GATA-1, Fli-1, and Sp1. J Biol Chem 2002;277:48333–48341.

    CAS  PubMed  Google Scholar 

  22. Zauli G, Bassini A, Vitale M, et al. Thrombopoietin enhances the alpha IIb beta 3-dependent adhesion of megakaryocytic cells to fibrinogen or fibronectin through PI 3 kinase. Blood 1997;89:883–895.

    CAS  PubMed  Google Scholar 

  23. Cui L, Ramsfjell V, Borge OJ, Veiby OP, Lok S, Jacobsen SE. Thrombopoietin promotes adhesion of primitive human hemopoietic cells to fibronectin and vascular cell adhesion molecule-1: role of activation of very late antigen (VLA)-4 and VLA-5. J Immunol 1997;159:1961–1969.

    CAS  PubMed  Google Scholar 

  24. Geddis AE, Linden HM, Kaushansky K. Thrombopoietin: a pan-hematopoietic cytokine. Cytokine Growth Factor Rev 2002;13:61–73.

    CAS  PubMed  Google Scholar 

  25. Hoffman RC, Andersen H, Walker K, et al. Peptide, disulfide, and glycosylation mapping of recombinant human thrombopoietin from Ser1 to Arg246. Biochemistry 1996;35:14849–14861.

    CAS  PubMed  Google Scholar 

  26. Pearce KH, Jr., Potts BJ, Presta LG, Bald LN, Fendly BM, Wells JA. Mutational analysis of thrombopoietin for identification of receptor and neutralizing antibody sites. J Biol Chem 1997;272:20595–20602.

    CAS  PubMed  Google Scholar 

  27. Foster D, Hunt P. The biological significance of truncated and full-length forms of mpl ligand. In: Kuter DJ, Hunt P, Sheridan W, Zucker-Franklin D, eds. Thrombopoiesis and Thrombopoietins: Molecular, cellular, preclinical and clinical biology. Totowa, NJ: Humana Press Inc.; 1997:203–214.

    Google Scholar 

  28. Gurney 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.

    CAS  PubMed  Google Scholar 

  29. Chang MS, McNinch J, Basu R, et al. Cloning and characterization of the human megakaryocyte growth and development factor (MGDF) gene. J Biol Chem 1995;270:511–514.

    CAS  PubMed  Google Scholar 

  30. Sasaki Y, Takahashi T, Miyazaki H, et al. Production of thrombopoietin by human carcinomas and its novel isoforms. Blood 1999;94:1952–1960.

    CAS  PubMed  Google Scholar 

  31. Stoffel R, Wiestner A, Skoda RC. Thrombopoietin in thrombocytopenic mice: evidence against regulation at the mRNA level and for a direct regulatory role of platelets. Blood 1996;87:567–573.

    CAS  PubMed  Google Scholar 

  32. Muto T, Feese MD, Shimada Y, et al. Functional analysis of the C-terminal region of recombinant human thrombopoietin. C-terminal region of thrombopoietin is a “shuttle” peptide to help secretion. J Biol Chem 2000;275:12090–12094.

    CAS  PubMed  Google Scholar 

  33. Li B, Pan H, Winkelmann JC, Dai W. Thrombopoietin and its alternatively spliced form are expressed in human amygdala and hippocampus. Blood 1996;87:5382–5384.

    CAS  PubMed  Google Scholar 

  34. Dame C, Wolber EM, Freitag P, Hofmann D, Bartmann P, Fandrey J. Thrombopoietin gene expression in the developing human central nervous system. Brain Res Dev Brain Res 2003;143:217–223.

    CAS  PubMed  Google Scholar 

  35. Sola MC, Juul SE, Meng YG, et al. Thrombopoietin (Tpo) in the fetus and neonate: Tpo concentrations in preterm and term neonates, and organ distribution of Tpo and its receptor (c-mpl) during human fetal development. Early Hum Dev 1999;53:239–250.

    CAS  PubMed  Google Scholar 

  36. Wolber EM, Dame C, Fahnenstich H, Hofmann D, Bartmann P, Jelkmann W, Fandrey J. Expression of the thrombopoietin gene in human fetal and neonatal tissues. Blood 1999;94:97–105.

    CAS  PubMed  Google Scholar 

  37. Sungaran R, Markovic B, Chong BH. Localization and regulation of thrombopoietin mRNa expression in human kidney, liver, bone marrow, and spleen using in situ hybridization. Blood 1997;89:101–107.

    CAS  PubMed  Google Scholar 

  38. Dame C, Fahnenstich H, Freitag P, et al. Erythropoietin mRNA expression in human fetal and neonatal tissue. Blood 1998;92:3218–3225.

    CAS  PubMed  Google Scholar 

  39. Mignotte V, Vigon I, Boucher de Crevecoeur E, Romeo PH, Lemarchandel V, Chretien S. Structure and transcription of the human c-mpl gene (MPL). Genomics 1994;20:5–12.

    CAS  PubMed  Google Scholar 

  40. Sabath DF, Kaushansky K, Broudy VC. Deletion of the extracellular membrane-distal cytokine receptor homology module of Mpl results in constitutive cell growth and loss of thrombopoietin binding. Blood 1999;94:365–367.

    CAS  PubMed  Google Scholar 

  41. Drachman JG, Miyakawa Y, Luthi JN, et al. Studies with chimeric Mpl/JAK2 receptors indicate that both JAK2 and the membrane-proximal domain of Mpl are required for cellular proliferation. J Biol Chem 2002;277:23544–23553.

    CAS  PubMed  Google Scholar 

  42. Drachman JG, Kaushansky K. Dissecting the thrombopoietin receptor: functional elements of the Mpl cytoplasmic domain. Proc Natl Acad Sci USA 1997;94:2350–2355.

    CAS  PubMed  Google Scholar 

  43. Fielder PJ, Gurney AL, Stefanich E, et al. Regulation of thrombopoietin levels by c-mpl-mediated binding to platelets. Blood 1996;87:2154–2161.

    CAS  PubMed  Google Scholar 

  44. Skoda RC, Seldin DC, Chiang MK, 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;12:2645–2653.

    CAS  PubMed  Google Scholar 

  45. Debili N, Wendling F, Cosman D, et al. The Mpl receptor is expressed in the megakaryocytic lineage from late progenitors to platelets. Blood 1995;85:391–401.

    CAS  PubMed  Google Scholar 

  46. Nakanishi K, Tajima F, Osada H, et al. Thrombopoietin expression in normal and hypobaric hypoxia-induced thrombocytopenic rats. Lab Invest 1999;79:679–688.

    CAS  PubMed  Google Scholar 

  47. Yang M, Xia WJ, Li K, et al. Identification of TPO Receptors on Central Nervous System-A Preliminary Report. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2004;12:494–497.

    CAS  PubMed  Google Scholar 

  48. Cohen-Solal K, Villeval JL, Titeux M, Lok S, Vainchenker W, Wendling F. Constitutive expression of Mpl ligand transcripts during thrombocytopenia or thrombocytosis. Blood 1996;88:2578–2584.

    CAS  PubMed  Google Scholar 

  49. Kuter DJ, Rosenberg RD. The reciprocal relationship of thrombopoietin (c-Mpl ligand) to changes in the platelet mass during busulfan-induced thrombocytopenia in the rabbit. Blood 1995;85:2720–2730.

    CAS  PubMed  Google Scholar 

  50. Ichikawa N, Ishida F, Shimodaira S, Tahara T, Kato T, Kitano K. Regulation of serum thrombopoietin levels by platelets and megakaryocytes in patients with aplastic anaemia and idiopathic thrombocytopenic purpura. Thromb Haemost 1996;76:156–160.

    CAS  PubMed  Google Scholar 

  51. Cremer M, Dame C, Schaeffer HJ, Giers G, Bartmann P, Bald R. Longitudinal thrombopoietin plasma concentrations in fetuses with alloimmune thrombocytopenia treated with intrauterine PLT transfusions. Transfusion 2003;43:1216–1222.

    CAS  PubMed  Google Scholar 

  52. Hsu HC, Tsai WH, Jiang ML, et al. Circulating levels of thrombopoietic and inflammatory cytokines in patients with clonal and reactive thrombocytosis. J Lab Clin Med 1999;134:392–397.

    CAS  PubMed  Google Scholar 

  53. Cerutti A, Custodi P, Mduranti, Cazzola M, Balduini CL. Circulating thrombopoietin in reactive conditions behaves like an acute phase reactant. Clin Lab Haematol 1999;21:271–275.

    CAS  PubMed  Google Scholar 

  54. Ishiguro A, Suzuki Y, Mito M, et al. Elevation of serum thrombopoietin precedes thrombocytosis in acute infections. Br J Haematol 2002;116:612–618.

    CAS  PubMed  Google Scholar 

  55. Wolber EM, Jelkmann W. Interleukin-6 increases thrombopoietin production in human hepatoma cells HepG2 and Hep3B. J Interferon Cytokine Res 2000;20:499–506.

    CAS  PubMed  Google Scholar 

  56. Kaser A, Brandacher G, Steurer W, et al. Interleukin-6 stimulates thrombopoiesis through thrombopoietin: role in inflammatory thrombocytosis. Blood 2001;98:2720–2725.

    CAS  PubMed  Google Scholar 

  57. Cardier JE, Dempsey J. Thrombopoietin and its receptor, c-mpl, are constitutively expressed by mouse liver endothelial cells: evidence of thrombopoietin as a growth factor for liver endothelial cells. Blood 1998;91:923–929.

    CAS  PubMed  Google Scholar 

  58. Wolber EM, Fandrey J, Frackowski U, Jelkmann W. Hepatic thrombopoietin mRNA is increased in acute inflammation. Thromb Haemost 2001;86:1421–1424.

    CAS  PubMed  Google Scholar 

  59. Yamashita K, Matsuoka H, Ochiai T, et al. Hepatocyte growth factor/scatter factor enhances the thrombopoietin mRNA expression in rat hepatocytes and cirrhotic rat livers. J Gastroenterol Hepatol 2000;15:83–90.

    CAS  PubMed  Google Scholar 

  60. Nagata Y, Shozaki Y, Nagahisa H, Nagasawa T, Abe T, Todokoro K. Serum thrombopoietin level is not regulated by transcription but by the total counts of both megakaryocytes and platelets during thrombocytopenia and thrombocytosis. Thromb Haemost 1997;77:808–814.

    CAS  PubMed  Google Scholar 

  61. Dame C. Developmental biology of thrombopoietin in the human fetus and neonate. Acta Paediatr Suppl 2002;91:54–65.

    CAS  PubMed  Google Scholar 

  62. Folman CC, von dem Borne AE, Rensink IH, et al. Sensitive measurement of thrombopoietin by a monoclonal antibody based sandwich enzymelinked immunosorbent assay. Thromb Haemost 1997;78:1262–1267.

    CAS  PubMed  Google Scholar 

  63. Ikeno K, Koike K, Takeshita A, et al. Stressful delivery influences circulating thrombopoietin (TPO) levels in newborns: possible role for cortisol in TPO-mpl binding. Early Hum Dev 2000;58:225–235.

    CAS  PubMed  Google Scholar 

  64. Ishiguro A, Nakahata T, Matsubara K, et al. Age-related changes in thrombopoietin in children: reference interval for serum thrombopoietin levels. Br J Haematol 1999;106:884–888.

    CAS  PubMed  Google Scholar 

  65. Albert TS, Meng YG, Simms P, Cohen RL, Phibbs RH. Thrombopoietin in the thrombocytopenic term and preterm newborn. Pediatrics 2000;105:1286–1291.

    CAS  PubMed  Google Scholar 

  66. Oygur N, Tunga M, Mumcu Y, et al. Thrombopoietin levels of thrombocytopenic term and preterm newborns with infection. Am J Perinatol 2001;18:279–286.

    CAS  PubMed  Google Scholar 

  67. Matsubara K, Baba K, Nigami H, et al. Early elevation of serum thrombopoietin levels and subsequent thrombocytosis in healthy preterm infants. Br J Haematol 2001;115:963–968.

    CAS  PubMed  Google Scholar 

  68. Murray NA, Watts TL, Roberts IA. Endogenous thrombopoietin levels and effect of recombinant human thrombopoietin on megakaryocyte precursors in term and preterm babies. Pediatr Res 1998;43:148–151.

    CAS  PubMed  Google Scholar 

  69. Watts TL, Murray NA, Roberts IA. Thrombopoietin has a primary role in the regulation of platelet production in preterm babies. Pediatr Res 1999;46:28–32.

    CAS  PubMed  Google Scholar 

  70. Sola MC, Calhoun DA, Hutson AD, Christensen RD. Plasma thrombopoietin concentrations in thrombocytopenic and non-thrombocytopenic patients in a neonatal intensive care unit. Br J Haematol 1999;104:90–92.

    CAS  PubMed  Google Scholar 

  71. Colarizi P, Fiorucci P, Caradonna A, Ficuccilli F, Mancuso M, Papoff P. Circulating thrombopoietin levels in neonates with infection. Acta Paediatr 1999;88:332–337.

    CAS  PubMed  Google Scholar 

  72. Dame C, Cremer M, Ballmaier M, et al. Concentrations of thrombopoietin and interleukin-11 in the umbilical cord blood of patients with fetal alloimmune thrombocytopenia. Am J Perinatol 2001;18:335–344.

    CAS  PubMed  Google Scholar 

  73. Sainio S, Javela K, Kekomaki R, Teramo K. Thrombopoietin levels in cord blood plasma and amniotic fluid in fetuses with alloimmune thrombocytopenia and healthy controls. Br J Haematol 2000;109:330–335.

    CAS  PubMed  Google Scholar 

  74. Jilma-Stohlawetz P, Homoncik M, Jilma B, et al. High levels of reticulated platelets and thrombopoietin characterize fetal thrombopoiesis. Br J Haematol 2001;112:466–468.

    CAS  PubMed  Google Scholar 

  75. Porcelijn L, Folman CC, de Haas M, et al. Fetal and neonatal thrombopoietin levels in alloimmune thrombocytopenia. Pediatr Res 2002;52:105–108.

    CAS  PubMed  Google Scholar 

  76. Dame C, Fahnenstich H, Schaaff F, Schild R, Bartmann P. Longitudinal determinations of fetal thrombopoietin concentrations in severe Rhesus hemolytic disease. Pediatric Research 2000;47:332A (abstract).

    Google Scholar 

  77. Walka MM, Sonntag J, Dudenhausen JW, Obladen M. Thrombopoietin concentration in umbilical cord blood of healthy term newborns is higher than in adult controls. Biol Neonate 1999;75:54–58.

    CAS  PubMed  Google Scholar 

  78. Ballmaier M, Schulze H, Strauss G, et al. Thrombopoietin in patients with congenital thrombocytopenia and absent radii: elevated serum levels, normal receptor expression, but defective reactivity to thrombopoietin. Blood 1997;90:612–619.

    CAS  PubMed  Google Scholar 

  79. Sekine I, Hagiwara T, Miyazaki H, et al. Thrombocytopenia with absent radii syndrome: studies on serum thrombopoietin levels and megakaryopoiesis in vitro. J Pediatr Hematol Oncol 1998;20:74–78.

    CAS  PubMed  Google Scholar 

  80. Cremer M, Schulze H, Linthorst G, et al. Serum levels of thrombopoietin, IL-11, and IL-6 in pediatric thrombocytopenias. Ann Hematol 1999;78:401–407.

    CAS  PubMed  Google Scholar 

  81. al-Jefri AH, Dror Y, Bussel JB, Freedman MH. Thrombocytopenia with absent radii: frequency of marrow megakaryocyte progenitors, proliferative characteristics, and megakaryocyte growth and development factor responsiveness. Pediatr Hematol Oncol 2000;17:299–306.

    CAS  PubMed  Google Scholar 

  82. Letestu R, Vitrat N, Masse A, et al. Existence of a differentiation blockage at the stage of a megakaryocyte precursor in the thrombocytopenia and absent radii (TAR) syndrome. Blood 2000;95:1633–1641.

    CAS  PubMed  Google Scholar 

  83. Strippoli P, Savoia A, Iolascon A, et al. Mutational screening of thrombopoietin receptor gene (c-mpl) in patients with congenital thrombocytopenia and absent radii (TAR). Br J Haematol 1998;103:311–314.

    CAS  PubMed  Google Scholar 

  84. Fleischman RA, Letestu R, Mi X, et al. Absence of mutations in the HoxA10, HoxA11 and HoxD11 nucleotide coding sequences in thrombocytopenia with absent radius syndrome. Br J Haematol 2002;116:367–375.

    CAS  PubMed  Google Scholar 

  85. Hedberg VA, Lipton JM. Thrombocytopenia with absent radii. A review of 100 cases. Am J Pediatr Hematol Oncol 1988;10:51–64.

    CAS  PubMed  Google Scholar 

  86. Ballmaier M, Germeshausen M, Schulze H, et al. c-mpl mutations are the cause of congenital amegakaryocytic thrombocytopenia. Blood 2001;97:139–146.

    CAS  PubMed  Google Scholar 

  87. Muraoka K, Ishii E, Tsuji K, et al. Defective response to thrombopoietin and impaired expression of c-mpl mRNA of bone marrow cells in congenital amegakaryocytic thrombocytopenia. Br J Haematol 1997;96:287–292.

    CAS  PubMed  Google Scholar 

  88. Van Den Oudenrijn S, Bruin M, Folman CC, et al. Mutations in the thrombopoietin receptor, mpl, in children with congenital amegakaryocytic thrombocytopenia. Br J Haematol 2000;110:441–448.

    PubMed  Google Scholar 

  89. Ihara K, Ishii E, Eguchi M, et al. Identification of mutations in the c-mpl gene in congenital amegakaryocytic thrombocytopenia. Proc Natl Acad Sci USA 1999;96:3132–3136.

    CAS  PubMed  Google Scholar 

  90. Kirito K, Fox N, Kaushansky K. Thrombopoietin stimulates Hoxb4 expression: an explanation for the favorable effects of TPO on hematopoietic stem cells. Blood 2003;102:3172–3178.

    PubMed  Google Scholar 

  91. Kirito K, Fox N, Kaushansky K. Thrombopoietin induces HOXA9 nuclear transport in immature hematopoietic cells: potential mechanism by which the hormone favorably affects hematopoietic stem cells. Mol Cell Biol 2004;24:6751–6762.

    CAS  PubMed  Google Scholar 

  92. Zipursky A. Transient leukaemia—a benign form of leukaemia in newborn infants with trisomy 21. Br J Haematol 2003;120:930–938.

    PubMed  Google Scholar 

  93. Wechsler J, Greene M, McDevitt MA, et al. Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome. Nat Genet 2002;32:148–152.

    CAS  PubMed  Google Scholar 

  94. Gurbuxani S, Vyas P, Crispino JD. Recent insights into the mechanisms of myeloid leukemogenesis in Down syndrome. Blood 2004;103:399–406.

    CAS  PubMed  Google Scholar 

  95. Schwab M, Niemeyer C, Schwarzer U. Down syndrome, transient myeloproliferative disorder, and infantile liver fibrosis. Med Pediatr Oncol 1998;31:159–165.

    CAS  PubMed  Google Scholar 

  96. Ruchelli ED, Uri A, Dimmick JE, et al. Severe perinatal liver disease and Down syndrome: an apparent relationship. Hum Pathol 1991;22:1274–1280.

    CAS  PubMed  Google Scholar 

  97. Bonno M, Azuma E, Kawasaki H, et al. Thrombopoietin level is inversely related to blast count, not platelet number, in Down syndrome neonates with transient myeloproliferative disorder. Am J Hematol 1998;58:267–272.

    CAS  PubMed  Google Scholar 

  98. Koenig JM, Christensen RD. Neutropenia and thrombocytopenia in infants with Rh hemolytic disease. J Pediatr 1989;114:625–631.

    CAS  PubMed  Google Scholar 

  99. Saade GR, Moise KJ, Jr., Copel JA, Belfort MA, Carpenter RJ, Jr. Fetal platelet counts correlate with the severity of the anemia in red-cell alloimmunization. Obstet Gynecol 1993;82:987–991.

    CAS  PubMed  Google Scholar 

  100. Wagner T, Bernaschek G, Geissler K. Inhibition of megakaryopoiesis by Kell-related antibodies. N Engl J Med 2000;343:72.

    CAS  PubMed  Google Scholar 

  101. Brown EJ, Zipursky A. Isoimmune hemolytic disease. In: Nathan DG, Oski FA, eds. Hematology of infancy and childhood. Philadelphia: WB Saunders; 1987:44–73.

    Google Scholar 

  102. Wolber EM, Ganschow R, Burdelski M, Jelkmann W. Hepatic thrombopoietin mRNA levels in acute and chronic liver failure of childhood. Hepatology 1999;29:1739–1742.

    CAS  PubMed  Google Scholar 

  103. Paul DA, Leef KH, Taylor S, McKenzie S. Thrombopoietin in preterm infants: gestational age-dependent response. J Pediatr Hematol Oncol 2002;24:304–309.

    PubMed  Google Scholar 

  104. Sola MC, Dame C, Christensen RD. Toward a rational use of recombinant thrombopoietin in the neonatal intensive care unit. J Pediatr Hematol Oncol 2001;23:179–184.

    CAS  PubMed  Google Scholar 

  105. Roberts IA, Murray NA. Thrombocytopenia in the newborn. Curr Opin Pediatr. 2003;15:17–23.

    PubMed  Google Scholar 

  106. Sola MC, Du Y, Hutson AD, Christensen RD. Dose-response relationship of megakaryocyte progenitors from bone marrow and peripheral blood of thrombocytopenic neonates to recombinant thrombopoietin. Pediatr Res 1999;45:153A (abstract).

    Google Scholar 

  107. Sola MC, Christensen RD, Hutson AD, Tarantal AF. Pharmacokinetics, pharmacodynamics, and safety of administering pegylated recombinant megakaryocyte growth and development factor to newborn rhesus monkeys. Pediatr Res. 2000;47:208–214.

    CAS  PubMed  Google Scholar 

  108. Dame C, Sutor AH. Primary and secondary thrombocytosis in childhood. Br J Haematol. 2005;in press.

    Google Scholar 

  109. Li J, Yang C, Xia Y, Bertino A, Glaspy J, Roberts M, Kuter DJ. Thrombocytopenia caused by the development of antibodies to thrombopoietin. Blood 2001;98:3241–3248.

    CAS  PubMed  Google Scholar 

  110. Basser RL, O’Flaherty E, Green M, et al. Development of pancytopenia with neutralizing antibodies to thrombopoietin after multicycle chemotherapy supported by megakaryocyte growth and development factor. Blood 2002;99:2599–2602.

    CAS  PubMed  Google Scholar 

  111. Orita T, Tsunoda H, Yabuta N, et al. A novel therapeutic approach for thrombocytopenia by minibody agonist of the thrombopoietin receptor. Blood 2004; prepublished online, September 16.

    Google Scholar 

  112. Dame C, Juul SE, Christensen RD. The biology of erythropoietin in the central nervous system and its neurotrophic and neuroprotective potential. Biol Neonate 2001;79:228–235.

    CAS  PubMed  Google Scholar 

  113. Zhang SC, Fedoroff S. Modulation of microglia by stem cell factor. J Neurosci Res 1998;53:29–37.

    CAS  PubMed  Google Scholar 

  114. Dame C, Bartmann P, Wolber E, Fahnenstich H, Hofmann D, Fandrey J. Erythropoietin gene expression in different areas of the developing human central nervous system. Brain Res Dev Brain Res 2000;125:69–74.

    CAS  PubMed  Google Scholar 

  115. Juul SE, Anderson DK, Li Y, Christensen RD. Erythropoietin and erythropoietin receptor in the developing human central nervous system. Pediatr Res 1998;43:40–49.

    CAS  PubMed  Google Scholar 

  116. Marti HH, Wenger RH, Rivas LA, et al. Erythropoietin gene expression in human, monkey and murine brain. Eur J Neurosci 1996;8:666–676.

    CAS  PubMed  Google Scholar 

  117. Chin K, Yu X, Beleslin-Cokic B, et al. Production and processing of erythropoietin receptor transcripts in brain. Brain Res Mol Brain Res 2000;81:29–42.

    CAS  PubMed  Google Scholar 

  118. Knabe W, Knerlich F, Washausen S, et al. Expression patterns of erythropoietin and its receptor in the developing midbrain. Anat Embryol (Berl) 2004;207:503–512.

    CAS  PubMed  Google Scholar 

  119. Chikuma M, Masuda S, Kobayashi T, Nagao M, Sasaki R. Tissue-specific regulation of erythropoietin production in the murine kidney, brain, and uterus. Am J Physiol Endocrinol Metab 2000;279:E1242–E1248.

    CAS  PubMed  Google Scholar 

  120. Stolze I, Berchner-Pfannschmidt U, Freitag P, et al. Hypoxia-inducible erythropoietin gene expression in human neuroblastoma cells. Blood 2002;100:2623–2628.

    CAS  PubMed  Google Scholar 

  121. Lipton SA. Erythropoietin for neurologic protection and diabetic neuropathy. N Engl J Med 2004;350:2516–2517.

    CAS  PubMed  Google Scholar 

  122. Ehrenreich H, Hasselblatt M, Dembowski C, et al. Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med 2002;8:495–505.

    CAS  PubMed  Google Scholar 

  123. Li B, Dai W. Thrombopoietin and neurotrophins share a common domain. Blood 1995;86:1643–1644.

    CAS  PubMed  Google Scholar 

  124. Columbyova L, Loda M, Scadden DT. Thrombopoietin receptor expression in human cancer cell lines and primary tissues. Cancer Res 1995;55:3509–3512.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neonatology, Charité — Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, D

    Chr. Dame (Assistant Professor)

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  1. Chr. Dame
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Editors and Affiliations

  1. Sanquin Consulting Services and Academic Institute for International Development of Transfusion Medicine, Groningen, The Netherlands

    C. TH. Smit Sibinga

  2. Center for Cancer and Blood Disorders, Children’s National Medical Center, Washington DC, USA

    N. Luban

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© 2005 Springer

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Dame, C. (2005). Biology of Thrombopoietin In the Human Foetus and Neonate. In: Smit Sibinga, C.T., Luban, N. (eds) Neonatology and Blood Transfusion. Developments in Hematology and Immunology, vol 39. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-23600-1_4

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  • DOI: https://doi.org/10.1007/978-0-387-23600-1_4

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