Thpo

Summary

Gene Symbol: Thpo
Description: thrombopoietin
Alias: Mgdf, Mpllg, Tpo, Tpo1, Tpo2, Tpo3, Tpo4, C-mpl ligand, megakaryocyte colony-stimulating factor, megakaryocyte growth and development factor, myeloproliferative leukemia virus oncogene ligand
Species: mouse

Top Publications

  1. ncbi Normal platelets and megakaryocytes are produced in vivo in the absence of thrombopoietin
    S Bunting
    Department of Molecular Oncology, Genentech Inc, South San Francisco, CA 94080, USA
    Blood 90:3423-9. 1997
  2. pmc A hematopoietic growth factor, thrombopoietin, has a proapoptotic role in the brain
    Hannelore Ehrenreich
    Max Planck Institute of Experimental Medicine, Georg August University, 37075 Goettingen, Germany
    Proc Natl Acad Sci U S A 102:862-7. 2005
  3. ncbi A pathobiologic pathway linking thrombopoietin, GATA-1, and TGF-beta1 in the development of myelofibrosis
    Alessandro M Vannucchi
    Clinical Biochemistry, Istituto Superiore Sanita, Viale Regina Elena 299, 00161 Rome, Italy
    Blood 105:3493-501. 2005
  4. pmc Physiological regulation of early and late stages of megakaryocytopoiesis by thrombopoietin
    F J de Sauvage
    Department of Molecular Biology, Genentech Inc, South San Francisco, California 94080, USA
    J Exp Med 183:651-6. 1996
  5. ncbi Genomic structure, chromosomal localization, and conserved alternative splice forms of thrombopoietin
    A L Gurney
    Department of Molecular Biology, Genentech, Inc, San Francisco, CA 94080
    Blood 85:981-8. 1995
  6. pmc Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4+ hemangiocytes
    David K Jin
    Department of Genetic Medicine, Division of Hematology Medical Oncology, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10021, USA
    Nat Med 12:557-67. 2006
  7. ncbi Thrombopoietin and the c-Mpl receptor: insights from gene targeting
    W S Alexander
    Walter and Eliza Hall Institute for Medical Research, Melbourne, Vic, Australia
    Int J Biochem Cell Biol 31:1027-35. 1999
  8. doi Diurnal expression of the thrombopoietin gene is regulated by CLOCK
    C J Tracey
    University BHF Centre for Cardiovascular Science, Queen s Medical Research Institute, University of Edinburgh, Edinburgh, UK
    J Thromb Haemost 10:662-9. 2012
  9. pmc Fundamental differences in endoreplication in mammals and Drosophila revealed by analysis of endocycling and endomitotic cells
    Noa Sher
    Whitehead Institute, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 110:9368-73. 2013
  10. ncbi Transgenic mice overexpressing murine thrombopoietin develop myelofibrosis and osteosclerosis
    Haruko Kakumitsu
    The First Department of Internal Medicine, Kyushu University Hospital, 3 1 1 Maidashi, Fukuoka 812 8582, Japan
    Leuk Res 29:761-9. 2005

Research Grants

Scientific Experts

  • Anna Rita Migliaccio
  • Olaf Hoffmann
  • Jose R Bayascas
  • Kenneth Kaushansky
  • Warren S Alexander
  • JANIS ABKOWITZ
  • Hannelore Ehrenreich
  • O Psenak
  • Anne Van der Meeren
  • BRIAN JOSEPH LANNUTTI
  • Keita Kirito
  • Norma Fox
  • Natalija Buza-Vidas
  • Noa Sher
  • Shahin Rafii
  • Hideki Amano
  • Hans Georg Kopp
  • F J de Sauvage
  • C J Tracey
  • Qiao jun Li
  • Daisuke Sugiyama
  • Anthony Rongvaux
  • Charlotta Böiers
  • Anna Ivanova
  • Song Chou
  • Christina T Jensen
  • Sten Eirik W Jacobsen
  • Bryan McIntosh
  • Kozue Yoshida
  • Masamichi Eguchi
  • Charlene F Barroga
  • Ian S Hitchcock
  • Katya Ravid
  • Harvey F Lodish
  • Jun Seita
  • Haruko K Shimoda
  • Norio Komatsu
  • Satoshi Takaki
  • Mine Harada
  • David K Jin
  • Tadashi Matsuda
  • Kenjirou Kamezaki
  • Kazuya Shimoda
  • Andrea T Hooper
  • Ronald G Crystal
  • Neil R Hackett
  • Fan Zhang
  • Scott T Avecilla
  • Sergey V Shmelkov
  • Alessandro M Vannucchi
  • Helen Burmester
  • Haruko Kakumitsu
  • Wei Tong
  • Xiaodong Xie
  • D L Eaton
  • K Carver-Moore
  • Yulia Kaluzhny
  • Hannah M Linden
  • Jessica R Von Stetina
  • Shinobu Matsuura
  • George W Bell
  • Terry L Orr-Weaver
  • X Q Yan
  • A J Harmar
  • M M Hussain
  • P S Hartley
  • X Pan
  • J H Catterson
  • Chiyo Mizuochi
  • Tim Willinger
  • George D Yancopoulos
  • David M Valenzuela
  • Andrew J Murphy
  • Chozhavendan Rathinam
  • Satoko Okayama
  • Elizabeth E Eynon
  • Kasem Kulkeaw
  • Wojtek Auerbach
  • Hitoshi Takizawa
  • Richard A Flavell
  • Markus G Manz
  • Sean Stevens
  • Li Ping Zou
  • Yuka Horio
  • Jian Wen Wang
  • Anne Hultquist
  • Juan Zhang
  • Jens Wuerfel
  • Matthias Ballmaier
  • Lilian Wittmann

Detail Information

Publications64

  1. ncbi Normal platelets and megakaryocytes are produced in vivo in the absence of thrombopoietin
    S Bunting
    Department of Molecular Oncology, Genentech Inc, South San Francisco, CA 94080, USA
    Blood 90:3423-9. 1997
    Thrombopoietin (TPO) has been established as the major regulator of megakaryocyte and platelet production. In vitro and in vivo studies have demonstrated that TPO affects both megakaryocyte proliferation and maturation...
  2. pmc A hematopoietic growth factor, thrombopoietin, has a proapoptotic role in the brain
    Hannelore Ehrenreich
    Max Planck Institute of Experimental Medicine, Georg August University, 37075 Goettingen, Germany
    Proc Natl Acad Sci U S A 102:862-7. 2005
    Central nervous and hematopoietic systems share developmental features. We report that thrombopoietin (TPO), a stimulator of platelet formation, acts in the brain as a counterpart of erythropoietin (EPO), a hematopoietic growth factor ..
  3. ncbi A pathobiologic pathway linking thrombopoietin, GATA-1, and TGF-beta1 in the development of myelofibrosis
    Alessandro M Vannucchi
    Clinical Biochemistry, Istituto Superiore Sanita, Viale Regina Elena 299, 00161 Rome, Italy
    Blood 105:3493-501. 2005
    ..Mice harboring genetic alterations in either the extrinsic (ectopic thrombopoietin expression, TPO(high) mice) or intrinsic (hypomorphic GATA-1 mutation, GATA-1(low) mice) control of Mk differentiation develop ..
  4. pmc Physiological regulation of early and late stages of megakaryocytopoiesis by thrombopoietin
    F J de Sauvage
    Department of Molecular Biology, Genentech Inc, South San Francisco, California 94080, USA
    J Exp Med 183:651-6. 1996
    Thrombopoietin (TPO) has recently been cloned and shown to regulate megakaryocyte and platelet production by activating the cytokine receptor c-mpl...
  5. ncbi Genomic structure, chromosomal localization, and conserved alternative splice forms of thrombopoietin
    A L Gurney
    Department of Molecular Biology, Genentech, Inc, San Francisco, CA 94080
    Blood 85:981-8. 1995
    Thrombopoietin (TPO), the ligand for c-mpl, is a novel cytokine comprising an amino terminal domain with homology to erythropoietin and a glycosylated carboxyl terminal domain that does not bear overall homology to other known proteins...
  6. pmc Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4+ hemangiocytes
    David K Jin
    Department of Genetic Medicine, Division of Hematology Medical Oncology, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10021, USA
    Nat Med 12:557-67. 2006
    ..Soluble Kit-ligand (sKitL), thrombopoietin (TPO, encoded by Thpo) and, to a lesser extent, erythropoietin (EPO) and granulocyte-macrophage colony-stimulating factor (GM-CSF) ..
  7. ncbi Thrombopoietin and the c-Mpl receptor: insights from gene targeting
    W S Alexander
    Walter and Eliza Hall Institute for Medical Research, Melbourne, Vic, Australia
    Int J Biochem Cell Biol 31:1027-35. 1999
    The availability of thrombopoietin (TPO) in recombinant form has revolutionized the study of megakaryocytopoiesis and provided an exciting new reagent for clinical evaluation...
  8. doi Diurnal expression of the thrombopoietin gene is regulated by CLOCK
    C J Tracey
    University BHF Centre for Cardiovascular Science, Queen s Medical Research Institute, University of Edinburgh, Edinburgh, UK
    J Thromb Haemost 10:662-9. 2012
    ..In addition, many cell types express endogenous circadian rhythms that affect cell-specific processes. Independent reports support the hypothesis that thrombopoietin (TPO) is under circadian control.
  9. pmc Fundamental differences in endoreplication in mammals and Drosophila revealed by analysis of endocycling and endomitotic cells
    Noa Sher
    Whitehead Institute, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 110:9368-73. 2013
    ..Consistent with TGCs endocycling rather than undergoing endomitosis, they have low expression of M-phase genes...
  10. ncbi Transgenic mice overexpressing murine thrombopoietin develop myelofibrosis and osteosclerosis
    Haruko Kakumitsu
    The First Department of Internal Medicine, Kyushu University Hospital, 3 1 1 Maidashi, Fukuoka 812 8582, Japan
    Leuk Res 29:761-9. 2005
    Thrombopoietin (TPO) regulates megakaryocytopoiesis and platelet production in vivo and in vitro. Exogenous overexpression of TPO in vivo by viral-mediated gene transfer induced bone marrow (BM) fibrosis and osteosclerosis...
  11. ncbi Thrombopoietin gene transfer-mediated enhancement of angiogenic responses to acute ischemia
    Hideki Amano
    Department of Genetic Medicine, Weill Medical College, Cornell University, New York, NY 10021, USA
    Circ Res 97:337-45. 2005
    ..Platelet levels are controlled by circulating levels of thrombopoietin (TPO) functioning to activate megakaryocyte differentiation and platelet release through the c-mpl receptor...
  12. pmc Tie2 activation contributes to hemangiogenic regeneration after myelosuppression
    Hans Georg Kopp
    Department of Genetic Medicine and Division of Hematology Oncology, Weill Medical College of Cornell University, 1300 York Ave, Room D601, New York, NY 10021, USA
    Blood 106:505-13. 2005
    ..Angiopoietins may be clinically useful to accelerate hemangiogenic recovery after myelosuppression...
  13. ncbi Hypomorphic mutation of PDK1 suppresses tumorigenesis in PTEN(+/-) mice
    Jose R Bayascas
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom
    Curr Biol 15:1839-46. 2005
    ....
  14. pmc Thrombopoietin enhances expression of vascular endothelial growth factor (VEGF) in primitive hematopoietic cells through induction of HIF-1alpha
    Keita Kirito
    Department of Medicine, Division of Hematology Oncology, University of California San Diego, San Diego, CA, USA
    Blood 105:4258-63. 2005
    Thrombopoietin (TPO), the primary regulator of thrombopoiesis, is also an important, nonredundant mediator of hematopoietic stem cell (HSC) development...
  15. pmc Cytokines regulate postnatal hematopoietic stem cell expansion: opposing roles of thrombopoietin and LNK
    Natalija Buza-Vidas
    Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Sweden
    Genes Dev 20:2018-23. 2006
    ..Herein, we identify thrombopoietin (THPO) and the cytokine signaling inhibitor LNK, as opposing physiological regulators of HSC expansion...
  16. pmc Lnk inhibits Tpo-mpl signaling and Tpo-mediated megakaryocytopoiesis
    Wei Tong
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    J Exp Med 200:569-80. 2004
    Thrombopoietin (Tpo) is the primary cytokine regulating megakaryocyte development and platelet production...
  17. pmc Lnk negatively regulates self-renewal of hematopoietic stem cells by modifying thrombopoietin-mediated signal transduction
    Jun Seita
    Laboratory of Stem Cell Therapy, Center for Experimental Medicine, University of Tokyo, 4 6 1 Shirokanedai, Tokyo 108 8639, Japan
    Proc Natl Acad Sci U S A 104:2349-54. 2007
    ..We show that Lnk negatively regulates self-renewal of HSCs by modifying thrombopoietin (TPO)-mediated signal transduction. Single-cell cultures showed that Lnk-deficient HSCs are hypersensitive to TPO...
  18. ncbi Thrombopoietin production in wild-type and interleukin-6 knockout mice with acute inflammation
    Helen Burmester
    Institute of Physiology, University of Luebeck, Luebeck, Germany
    J Interferon Cytokine Res 25:407-13. 2005
    Clinical and laboratory studies indicate that thrombopoietin (TPO) gene expression increases during inflammation...
  19. ncbi Role of thrombopoietin in mast cell differentiation
    Anna Rita Migliaccio
    Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanita, Viale Regina Elena 299, 00161 Rome, Italy
    Ann N Y Acad Sci 1106:152-74. 2007
    ..Some of the possible implications of this newly described biological activity of thrombopoietin will be discussed...
  20. pmc Studies of c-Mpl function distinguish the replication of hematopoietic stem cells from the expansion of differentiating clones
    Janis L Abkowitz
    Division of Hematology, Department of Medicine, University of Washington, Seattle, WA 98195 7710, USA
    Blood 109:5186-90. 2007
    ....
  21. doi Hepatoblasts comprise a niche for fetal liver erythropoiesis through cytokine production
    Daisuke Sugiyama
    Division of Hematopoietic Stem Cells, Advanced Medical Initiatives, Department of Advanced Medical Initiatives, Kyushu University Faculty of Medical Sciences, Fukuoka 812 8582, Japan
    Biochem Biophys Res Commun 410:301-6. 2011
    ..Our observations demonstrate that hepatoblasts comprise a niche for erythropoiesis through cytokine secretion...
  22. ncbi [Signal transduction pathway mediated by thrombopoietin in the inflammation model of microglia]
    Qiao jun Li
    Department of Pediatrics, First Affiliated Hospital of the People s Liberation Army General Hospital, Beijing 100048, China
    Zhongguo Dang Dai Er Ke Za Zhi 13:340-3. 2011
    BJECTIVE: To explore the signal transduction pathway mediated by thrombopoietin (TPO) in the inflammation model of microglia induced by lipopolysaccharide (LPS).
  23. pmc Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo
    Anthony Rongvaux
    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 108:2378-83. 2011
    ..Thrombopoietin (TPO) has been demonstrated as a crucial cytokine supporting maintenance and self-renewal of HSCs...
  24. pmc Thrombopoietin contributes to neuronal damage in experimental bacterial meningitis
    Olaf Hoffmann
    Department of Experimental Neurology, Charite Universitatsmedizin Berlin, Berlin, Germany
    Infect Immun 79:928-36. 2011
    Thrombopoietin (Tpo), which primarily regulates megakaryopoiesis, and its receptor (c-Mpl) are expressed in the brain, where Tpo exhibits proapototic effects on neurons...
  25. pmc Expression pattern of the thrombopoietin receptor (Mpl) in the murine central nervous system
    Anna Ivanova
    Department of Neonatology, Charite Universitatsmedizin, Germany
    BMC Dev Biol 10:77. 2010
    Thrombopoietin (Thpo) and its receptor (Mpl), which regulate megakaryopoiesis, are expressed in the central nervous system (CNS), where Thpo is thought to exert pro-apoptotic effects on newly generated neurons...
  26. doi Expression and role of FLT3 in regulation of the earliest stage of normal granulocyte-monocyte progenitor development
    Charlotta Böiers
    Hematopoietic Stem Cell Laboratory, Lund Stem Cell Center, Lund University, Lund, Sweden
    Blood 115:5061-8. 2010
    ..Notably, mice deficient in both thrombopoietin (THPO) and FL had a more pronounced GMP phenotype than Thpo(-/-) mice, establishing a role of FL in THPO-dependent and -..
  27. pmc Fetal liver hepatic progenitors are supportive stromal cells for hematopoietic stem cells
    Song Chou
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 107:7799-804. 2010
    ..Thus SCF(+)DLK(+) cells are a highly homogenous population that express a complete set of factors for HSC expansion and are likely the primary stromal cells that support HSC expansion in the fetal liver...
  28. pmc Thrombopoietin regulates c-Myb expression by modulating micro RNA 150 expression
    Charlene F Barroga
    Department of Medicine and Division of Hematology Oncology, University of California, San Diego School of Medicine, San Diego, CA 92103 8811, USA
    Exp Hematol 36:1585-92. 2008
    ..Micro RNAs (miRs) downregulate gene expression by binding to the 3' untranslated region (UTR) of specific messenger RNAs (mRNAs); we noted that the 3'UTR of c-Myb contains four miR-150 binding sites...
  29. doi Lesion-targeted thrombopoietin potentiates vasculogenesis by enhancing motility and enlivenment of transplanted endothelial progenitor cells via activation of Akt/mTOR/p70S6kinase signaling pathway
    Masamichi Eguchi
    Department of Regenerative Medicine, Tokai University School of Medicine, Japan
    J Mol Cell Cardiol 45:661-9. 2008
    Thrombopoietin (TPO), a physiological regulator of megakaryocyte and platelet development, is a multifunctional positive regulator in early hematopoiesis by hematopoietic stem cells...
  30. doi Thrombopoietin (TPO) regulates HIF-1alpha levels through generation of mitochondrial reactive oxygen species
    Kozue Yoshida
    Department of Hematology, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409 3898, Japan
    Int J Hematol 88:43-51. 2008
    ..In a previous study we found that thrombopoietin (TPO), an important and non-redundant cytokine for HSC maintenance and expansion, induces HIF-1alpha expression in HSCs ..
  31. pmc Transcriptional regulation of bone marrow thrombopoietin by platelet proteins
    Bryan McIntosh
    Department of Medicine, University of California San Diego, San Diego, CA 92103 8811, USA
    Exp Hematol 36:799-806. 2008
    Platelet production is regulated primarily by the cytokine thrombopoietin (TPO)...
  32. pmc Roles of focal adhesion kinase (FAK) in megakaryopoiesis and platelet function: studies using a megakaryocyte lineage specific FAK knockout
    Ian S Hitchcock
    Department of Medicine, University of California San Diego, La Jolla 92093, USA
    Blood 111:596-604. 2008
    ..Thrombopoietin (Tpo)-mediated activation of Lyn kinase, a negative regulator of megakaryopoiesis, is severely attenuated in FAK-null ..
  33. ncbi Chronic thrombopoietin overexpression induces mesangioproliferative glomerulopathy in mice
    Haruko K Shimoda
    Department of Internal Medicine, Gastroenterology and Hematology, Faculty of Medicine, Miyazaki University, Kiyotake, Miyazaki, Japan
    Am J Hematol 82:802-6. 2007
    We previously reported that mice transgenic (Tg) for thrombopoietin (TPO) developed progressive fibrosis and osteosclerosis of the bone marrow...
  34. pmc Thrombopoietin induces HOXA9 nuclear transport in immature hematopoietic cells: potential mechanism by which the hormone favorably affects hematopoietic stem cells
    Keita Kirito
    Department of Medicine, University of California San Diego School of Medicine, 402 Dickinson St, Suite 380, San Diego, CA 92103 8811, USA
    Mol Cell Biol 24:6751-62. 2004
    ..In our previous studies we demonstrated that thrombopoietin (TPO) enhances levels of HOXB4 mRNA in primitive hematopoietic cells (K. Kirito, N. Fox, and K...
  35. ncbi Lyn tyrosine kinase regulates thrombopoietin-induced proliferation of hematopoietic cell lines and primary megakaryocytic progenitors
    Brian J Lannutti
    Puget Sound Blood Center, Seattle, WA 98104 1256, USA
    Blood 103:3736-43. 2004
    In this study we demonstrate that thrombopoietin (TPO)-stimulated Src family kinases (SFKs) inhibit cellular proliferation and megakaryocyte differentiation...
  36. ncbi Constitutive expression of Mpl ligand transcripts during thrombocytopenia or thrombocytosis
    K Cohen-Solal
    INSERM U 362, Institut Gustave Roussy, Villejuif, France
    Blood 88:2578-84. 1996
    Mpl ligand (thrombopoietin [TPO]) is the physiological regulator of platelet production. In mice, mRNA encoding the Mpl ligand (Mpl-L) is predominantly found by Northern blot analysis in the liver and kidney...
  37. pmc Thrombopoietin rescues in vitro erythroid colony formation from mouse embryos lacking the erythropoietin receptor
    M W Kieran
    Department of Pediatrics, Children s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 93:9126-31. 1996
    ..yolk sac, peripheral blood, and fetal liver demonstrated near normal transcripts levels for EKLF, thrombopoietin (Tpo), c-MPL, GATA-1, GATA-2, and alpha- and embryonic beta H1-globin but non for adult beta maj-globin...
  38. ncbi Ectopic expression of murine TPO receptor (c-mpl) in mice is pathogenic and induces erythroblastic proliferation
    L Cocault
    INSERM U 363, Institut Cochin de Genetique Moleculaire, Hopital Cochin, Paris, France
    Blood 88:1656-65. 1996
    ..This study shows for the first time that ectopic expression of a member of the cytokine receptor superfamily promotes hematopoietic progenitor cell proliferation and could play a role in leukemogenesis...
  39. ncbi Low levels of erythroid and myeloid progenitors in thrombopoietin-and c-mpl-deficient mice
    K Carver-Moore
    Department of Molecular Oncology, Genentech, Inc, South San Francisco, CA 94080, USA
    Blood 88:803-8. 1996
    Thrombopoietin (TPO), the ligand for the c-mpl receptor, has been shown to be the major regulator of platelet production...
  40. ncbi A model of myelofibrosis and osteosclerosis in mice induced by overexpressing thrombopoietin (mpl ligand): reversal of disease by bone marrow transplantation
    X Q Yan
    Department of Developmental Hematology, Amgen Inc, Thousand Oaks, CA 91320 1789, USA
    Blood 88:402-9. 1996
    We have previously shown that mice induced to overexpress thrombopoietin (TPO) by retroviral-mediated gene transfer into bone marrow (BM) cells develop myelofibrosis and osteosclerosis...
  41. ncbi Mapping of the mouse Bcl6 gene to chromosome 16
    X Liao
    Mammalian Genetics Laboratory, ABL Basic Research Program, NCI Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA
    Mamm Genome 7:621-2. 1996
  42. ncbi Thrombopoietin, the ligand for the Mpl receptor, synergizes with steel factor and other early acting cytokines in supporting proliferation of primitive hematopoietic progenitors of mice
    H Ku
    Department of Medicine, Medical University of South Carolina, Charleston, USA
    Blood 87:4544-51. 1996
    ..Based on these observations, we propose that ML can function as an early acting cytokine and stimulate the proliferation of cell cycle dormant progenitors by shortening their G0 period...
  43. ncbi Chronic exposure to retroviral vector encoded MGDF (mpl-ligand) induces lineage-specific growth and differentiation of megakaryocytes in mice
    X Q Yan
    Department of Developmental Hematology, Amgen Inc, Thousand Oaks, CA 91320 1789, USA
    Blood 86:4025-33. 1995
    b>Megakaryocyte growth and development factor (MGDF) has recently been identified as a ligand for the c-mpl receptor...
  44. ncbi Thrombopoietin in thrombocytopenic mice: evidence against regulation at the mRNA level and for a direct regulatory role of platelets
    R Stoffel
    Department of Pharmacology, University of Basel, Switzerland
    Blood 87:567-73. 1996
    Thrombopoietin (TPO), originally described as an activity in the serum of thrombocytopenic animals that leads to increased production of platelets, has recently been isolated and cloned...
  45. ncbi Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo
    S Lok
    ZymoGenetics Corporation, Seattle, Washington 98105
    Nature 369:565-8. 1994
    ..These results along with those presented in the accompanying report strongly suggest that the ligand for c-Mpl is thrombopoietin...
  46. ncbi Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor Mpl
    T D Bartley
    Amgen, Incorporated, Amgen Center, Thousand Oaks, California 91320
    Cell 77:1117-24. 1994
    A novel megakaryocyte growth and development factor (MGDF) has been identified in aplastic canine plasma, and its cDNAs have been cloned from canine, murine, and human sources...
  47. pmc Thrombopoietin activates a STAT5-like factor in hematopoietic cells
    C Pallard
    U363 INSERM, ICGM, Hopital Cochin, Paris, France
    EMBO J 14:2847-56. 1995
    Thrombopoietin (TPO) is a newly cloned cytokine which is the major regulator of circulating platelet levels, acting on both proliferation and differentiation of megakaryocytes...
  48. ncbi Thrombopoietin: the primary regulator of megakaryocytopoiesis and thrombopoiesis
    D L Eaton
    Department of Cardiovascular Research, Genentech, So San Francisco, CA 94080, USA
    Exp Hematol 25:1-7. 1997
  49. ncbi Megakaryocytopoietic activity of a truncated variant of mouse thrombopoietin
    S Hoshi
    Tsukuba Research Laboratories, Eisai Co, Ltd, Ibaraki, Japan
    Biochem Biophys Res Commun 231:823-6. 1997
    Thrombopoietin (TPO) is a hemopoietic cytokine that specifically stimulates the growth and development of megakaryocytes...
  50. ncbi Cellular localization of thrombopoietin mRNA in the liver by in situ hybridization
    S Nomura
    Pharmaceutical Research Laboratory, Kirin Brewery Co, Ltd, Gunma, Japan
    Exp Hematol 25:565-72. 1997
    The expression of thrombopoietin (TPO) mRNA is observed in several tissues, including liver, kidney, brain, skeletal muscle, intestine, spleen, and bone marrow...
  51. ncbi Thrombopoietin stimulates Hoxb4 expression: an explanation for the favorable effects of TPO on hematopoietic stem cells
    Keita Kirito
    Department of Medicine, Division of Hematology Oncology, University of California, San Diego, 92103, USA
    Blood 102:3172-8. 2003
    Thrombopoietin (TPO), the primary regulator of platelet production, also plays an important role in hematopoietic stem cell (HSC) biology...
  52. ncbi Thrombopoietin promotes mixed lineage and megakaryocytic colony-forming cell growth but inhibits primitive and definitive erythropoiesis in cells isolated from early murine yolk sacs
    Xiaodong Xie
    Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis 46202, USA
    Blood 101:1329-35. 2003
    The role of thrombopoietin (Tpo) in promoting hematopoiesis has been extensively studied in late fetal, neonatal, and adult mice. However, the effects of Tpo on early yolk sac hematopoiesis have been largely unexplored...
  53. ncbi A selective effect of Mpl ligand on mRNA stabilization during megakaryocyte differentiation
    Yulia Kaluzhny
    Department of Biochemistry, K225, Boston University School of Medicine, 715 Albany St, Boston, MA 02118, USA
    FEBS Lett 527:279-83. 2002
    ..Our study is the first to suggest that Mpl ligand-induced lineage specification is also determined by message stabilization...
  54. pmc Thrombopoietin expands hematopoietic stem cells after transplantation
    Norma Fox
    University of California San Diego School of Medicine, Department of Medicine, San Diego, California 92103 8811, USA
    J Clin Invest 110:389-94. 2002
    Multiple lines of evidence indicate that thrombopoietin (TPO) contributes to the development of hematopoietic stem cells (HSC), supporting their survival and proliferation in vitro...
  55. ncbi The glycan domain of thrombopoietin (TPO) acts in trans to enhance secretion of the hormone and other cytokines
    Hannah M Linden
    Division of Hematology, University of Washington School of Medicine, Seattle, Washington 98195, USA
    J Biol Chem 277:35240-7. 2002
    Thrombopoietin (TPO), the primary regulator of platelet production, is composed of an amino-terminal 152 amino acids, sufficient for activity, and a carboxyl-terminal region rich in carbohydrates (183 residues) that enhances secretion of ..
  56. ncbi Administration of recombinant human IL11 after supralethal radiation exposure promotes survival in mice: interactive effect with thrombopoietin
    Anne Van der Meeren
    IPSN, DPHD, SARAM, B P no 6, F 92265 Fontenay aux Roses Cedex, France
    Radiat Res 157:642-9. 2002
    ..IL11 was administered along with thrombopoietin (TPO) or bone marrow transplantation to limit the hematopoietic syndrome, in addition to antibiotic treatment...
  57. ncbi Lineage-specific growth factors can compensate for stem and progenitor cell deficiencies at the postprogenitor cell level: an analysis of doubly TPO- and G-CSF receptor-deficient mice
    Kenneth Kaushansky
    University of Washington School of Medicine, Divisions of Hematology and Infectious Diseases, Seattle, WA 98195, USA
    Blood 99:3573-8. 2002
    Multiple lines of evidence indicate that thrombopoietin (TPO) substantially impacts the number of hematopoietic stem cells and progenitors of all myeloid lineages...
  58. ncbi Cytokine production and function in c-mpl-deficient mice: no physiologic role for interleukin-3 in residual megakaryocyte and platelet production
    T Gainsford
    The Walter and Eliza Hall Institute for Medical Research, PO Royal Melbourne Hospital, Victoria, Australia
    Blood 91:2745-52. 1998
    Mice lacking thrombopoietin (TPO), or its receptor c-Mpl, display defective megakaryocyte and platelet development and deficiencies in progenitor cells of multiple hematopoietic lineages...
  59. ncbi Hematopoietic deficiencies in c-mpl and TPO knockout mice
    M Murone
    Department of Molecular Oncology, Genentech, Inc, South San Francisco, California 94080, USA
    Stem Cells 16:1-6. 1998
    Thrombopoietin (TPO) is the primary regulatory of megakaryocyte (Meg) and platelet production. Its receptor, c-mpl, is a member of the cytokine receptor superfamily...
  60. ncbi The Mpl-ligand is involved in the growth-promoting activity of the murine stromal cell line MS-5 on ES cell-derived hematopoiesis
    M T Mitjavila
    INSERM U 362, Institut Gustave Roussy, Villejuif, France
    Exp Hematol 26:124-34. 1998
    ..Second, at a later stage of differentiation, the MS-5 cells promote hematopoiesis within EBs. Mpl-L appears to be one of the components that confer this latter ability on the MS-5 cell line...
  61. ncbi Thrombopoietin inhibits in vitro osteoclastogenesis from murine bone marrow cells
    T Wakikawa
    Department of Biochemistry, Osaka City University Medical School, Osaka, Japan
    Endocrinology 138:4160-6. 1997
    To determine whether thrombopoietin (TPO) can modulate the osteoclastic differentiation from hematopoietic stem cells, we investigated the effect of TPO on in vitro osteoclastogenesis by using the coculture of murine bone marrow cells ..
  62. ncbi The gene for murine megakaryocyte growth and development factor (thrombopoietin, Thpo) is located on mouse chromosome 16
    M S Chang
    Department of Developmental Biology, Amgen Inc, Thousand Oaks, California 91320, USA
    Genomics 26:636-7. 1995
  63. ncbi Cytokine gene expression in regenerating haematopoietic tissues of mice after cyclophosphamide treatment
    O Psenak
    Department of Pathophysiology, First Medical School, Charles University, Prague, Czech Republic
    Acta Haematol 109:68-75. 2003
    ..effect on HPC - stem cell factor (SCF), fetal liver tyrosine kinase 3-ligand (flt3-ligand), thrombopoietin (TPO), stromal cell-derived factor 1 (SDF-1), oncostatin M (OSM) -, a suppressive effect on HPC proliferation - ..
  64. pmc Human thrombopoietin: gene structure, cDNA sequence, expression, and chromosomal localization
    D C Foster
    ZymoGenetics Inc, Seattle, WA 98102
    Proc Natl Acad Sci U S A 91:13023-7. 1994
    Thrombopoietin (TPO), a lineage-specific cytokine affecting the proliferation and maturation of megakaryocytes from committed progenitor cells, is believed to be the major physiological regulator of circulating platelet levels...

Research Grants50

  1. KINETICS AND BEHAVIOR OF HEMOPOIETIC STEM CELLS
    JANIS ABKOWITZ; Fiscal Year: 2004
    ..By analyzing HSC kinetics in cats and mice, experimental systems with vastly different hemopoietic demands, we hope to gain insights that will allow an extrapolation to human hemopoiesis. ..
  2. FELINE LEUKEMIA VIRUS INDUCED RED CELL APLASIA
    JANIS ABKOWITZ; Fiscal Year: 2003
    ..abstract_text> ..
  3. The Kinetics and Behavior of Hematopoietic Stem cells
    JANIS ABKOWITZ; Fiscal Year: 2007
    ..Broadly, this application uses parabiosis, evolutionary analyses and stochastic simulation, 3 systems biology approaches, to gain insights into the in vivo behavior of HSC. ..
  4. The Kinetics and Behavior of Hematopoietic Stem cells
    JANIS ABKOWITZ; Fiscal Year: 2009
    ..Broadly, this application uses parabiosis, evolutionary analyses and stochastic simulation, 3 systems biology approaches, to gain insights into the in vivo behavior of HSC. ..
  5. Career Development in Clinical Hematology Research
    JANIS ABKOWITZ; Fiscal Year: 2007
    ..We anticipate that the scholars will progress to tenure track academic appointments at our institution or elsewhere. The broad goal of our application is to promote benign hematology clinical research, as this is an underserved field. ..
  6. Thrombopoietin Signaling: The Role of Src Kinases
    BRIAN LANNUTTI; Fiscal Year: 2007
    ..of this project are to gain insight into the signal transduction mechanisms of the growth factor thrombopoietin (TPO) and its receptor, Mp1, as well as provide the applicant, Brian Lannutti with the scientific tools and career ..
  7. Physiology of feline leukemia virus C receptor, FLVCR
    JANIS ABKOWITZ; Fiscal Year: 2009
    ..We anticipate that these studies will provide novel insights into a unique cell protection mechanism. ..
  8. Pathogenesis of clonal dominance in myelopoliferative d*
    JANIS ABKOWITZ; Fiscal Year: 2007
    ..We anticipate that, once validated, stochastic simulation will be an excellent tool for further studies of the pathogenesis of individual myeloproliferative diseases, disease progression and subclone evolution. ..
  9. IN UTERO TRANSPLANTATION FOR LYSOSOMAL STORAGE DISEASE
    JANIS ABKOWITZ; Fiscal Year: 2002
    ..The investigators are hopeful that these studies will provide alternative approaches for the therapy of lysosomal storage disorders. ..
  10. KINETICS AND BEHAVIOR OF HEMATOPOIETIC STEM CELLS
    JANIS ABKOWITZ; Fiscal Year: 1999
    ..Taken together, the PI believes these studies will provide insight into the kinetics and behavior of hematopoietic stem cells in large animals, to optimal strategies for gene therapy, and to disease pathogenesis. ..
  11. KINETICS AND BEHAVIOR OF HEMATOPOIETIC STEM CELLS
    JANIS ABKOWITZ; Fiscal Year: 1993
    ....
  12. FELINE LEUKEMIA VIRUS-INDUCED HEMATOLOGIC DISEASE
    JANIS ABKOWITZ; Fiscal Year: 1991
    ..This model will be generated through the repeated use of myelosuppressive drugs such as dimethylmyleran or through autologous bone marrow transplantation employing low numbers of hematopoietic cells...