MPL

Summary

Gene Symbol: MPL
Description: MPL proto-oncogene, thrombopoietin receptor
Alias: C-MPL, CD110, MPLV, THCYT2, TPOR, thrombopoietin receptor, TPO-R, myeloproliferative leukemia protein, myeloproliferative leukemia virus oncogene, proto-oncogene c-Mpl
Species: human

Top Publications

  1. ncbi Expression of the GPI-anchored receptor Prv-1 enhances thrombopoietin and IL-3-induced proliferation in hematopoietic cell lines
    Megan Dillon
    Puget Sound Blood Center, Seattle, WA 98104, United States
    Leuk Res 32:811-9. 2008
  2. pmc 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
    I Vigon
    Institut Cochin de Genetique Moleculaire, Institut National de la Santé et de la Recherche Médicale Unité 152, Hopital Cochin, Paris, France
    Proc Natl Acad Sci U S A 89:5640-4. 1992
  3. ncbi A putative truncated cytokine receptor gene transduced by the myeloproliferative leukemia virus immortalizes hematopoietic progenitors
    M Souyri
    INSERM U 152 Hôpital Cochin, Paris, France
    Cell 63:1137-47. 1990
  4. ncbi Structure and transcription of the human c-mpl gene (MPL)
    V Mignotte
    Institut National de la Sante et de la Recherche Medicale, U 91, Hopital Henri Mondor, Creteil, France
    Genomics 20:5-12. 1994
  5. ncbi Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand
    F J de Sauvage
    Department of Molecular Biology, Genentech, South San Francisco, California 94080
    Nature 369:533-8. 1994
  6. pmc Dissecting the thrombopoietin receptor: functional elements of the Mpl cytoplasmic domain
    J G Drachman
    Division of Hematology, University of Washington Medical Center, Seattle 98195, USA
    Proc Natl Acad Sci U S A 94:2350-5. 1997
  7. pmc Identification of mutations in the c-mpl gene in congenital amegakaryocytic thrombocytopenia
    K Ihara
    Department of Pediatrics, Faculty of Medicine, Kyushu University, Fukuoka 810 8582, Japan
    Proc Natl Acad Sci U S A 96:3132-6. 1999
  8. ncbi Thrombopoietin induces phosphoinositol 3-kinase activation through SHP2, Gab, and insulin receptor substrate proteins in BAF3 cells and primary murine megakaryocytes
    Y Miyakawa
    Division of Hematology, University of Washington School of Medicine, Seattle 98195, USA
    J Biol Chem 276:2494-502. 2001
  9. ncbi c-mpl mutations are the cause of congenital amegakaryocytic thrombocytopenia
    M Ballmaier
    Department of Pediatric Hematology and Oncology, Medizinische Hochschule Hannover, Germany
    Blood 97:139-46. 2001
  10. pmc Mpl Baltimore: a thrombopoietin receptor polymorphism associated with thrombocytosis
    Alison R Moliterno
    Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 101:11444-7. 2004

Research Grants

  1. MOLECULAR AND CELLULAR BIOLOGY OF THROMBOPOIETIN
    Kenneth Kaushansky; Fiscal Year: 2013
  2. Functional Studies of the Extracellular Domain of Mpl
    DANIEL SABATH; Fiscal Year: 2004
  3. Mechanism of Lnk function in cytokine receptor signaling
    Wei Tong; Fiscal Year: 2009
  4. THROMBOPOIETIN SIGNAL TRANSDUCTION
    Jonathan Drachman; Fiscal Year: 2000
  5. REGULATION OF HEMATOPOIESIS BY THROMBOPOIETIN
    Warren Alexander; Fiscal Year: 2001
  6. Inhibition of Histone Deacetylase in Myeloproliferative Neoplasms
    Golam Mohi; Fiscal Year: 2012
  7. Wei Tong; Fiscal Year: 2014
  8. Erythropoietin Blockade for the Treatment of Cancer
    C Anthony Blau; Fiscal Year: 2012
  9. Glen D Raffel; Fiscal Year: 2016
  10. Wei Tong; Fiscal Year: 2016

Detail Information

Publications236 found, 100 shown here

  1. ncbi Expression of the GPI-anchored receptor Prv-1 enhances thrombopoietin and IL-3-induced proliferation in hematopoietic cell lines
    Megan Dillon
    Puget Sound Blood Center, Seattle, WA 98104, United States
    Leuk Res 32:811-9. 2008
    ..In this study, we assessed the role of Prv-1 in thrombopoietin (Tpo)/Mpl signaling with the goal of identifying molecular mechanisms which augment Tpo-induced proliferation...
  2. pmc 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
    I Vigon
    Institut Cochin de Genetique Moleculaire, Institut National de la Santé et de la Recherche Médicale Unité 152, Hopital Cochin, Paris, France
    Proc Natl Acad Sci U S A 89:5640-4. 1992
    We have cloned the human homolog of the v-mpl oncogene transduced in the myeloproliferative leukemia retrovirus, which presents striking homologies with members of the hematopoietin receptor superfamily...
  3. ncbi A putative truncated cytokine receptor gene transduced by the myeloproliferative leukemia virus immortalizes hematopoietic progenitors
    M Souyri
    INSERM U 152 Hôpital Cochin, Paris, France
    Cell 63:1137-47. 1990
    The myeloproliferative leukemia virus (MPLV) is an acute leukemogenic murine replication-defective retrovirus...
  4. ncbi Structure and transcription of the human c-mpl gene (MPL)
    V Mignotte
    Institut National de la Sante et de la Recherche Medicale, U 91, Hopital Henri Mondor, Creteil, France
    Genomics 20:5-12. 1994
    The human c-mpl proto-oncogene encodes a member of the cytokine receptor superfamily, expressed mainly in CD 34-positive hematopoietic progenitors and in the megakaryocytic lineage...
  5. ncbi Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand
    F J de Sauvage
    Department of Molecular Biology, Genentech, South San Francisco, California 94080
    Nature 369:533-8. 1994
    ..This protein binds to and activates the c-mpl protein, a member of the cytokine receptor superfamily...
  6. pmc Dissecting the thrombopoietin receptor: functional elements of the Mpl cytoplasmic domain
    J G Drachman
    Division of Hematology, University of Washington Medical Center, Seattle 98195, USA
    Proc Natl Acad Sci U S A 94:2350-5. 1997
    Thrombopoietin (TPO) acts through its receptor, Mpl, to stimulate the proliferation and maturation of megakaryocytes and their progenitors...
  7. pmc Identification of mutations in the c-mpl gene in congenital amegakaryocytic thrombocytopenia
    K Ihara
    Department of Pediatrics, Faculty of Medicine, Kyushu University, Fukuoka 810 8582, Japan
    Proc Natl Acad Sci U S A 96:3132-6. 1999
    ..Our previous hematological analysis indicated similarities between human CAMT and murine c-mpl (thrombopoietin receptor) deficiency...
  8. ncbi Thrombopoietin induces phosphoinositol 3-kinase activation through SHP2, Gab, and insulin receptor substrate proteins in BAF3 cells and primary murine megakaryocytes
    Y Miyakawa
    Division of Hematology, University of Washington School of Medicine, Seattle 98195, USA
    J Biol Chem 276:2494-502. 2001
    ..The hormone acts by binding to the Mpl receptor, the product of the cellular proto-oncogene c-mpl...
  9. ncbi c-mpl mutations are the cause of congenital amegakaryocytic thrombocytopenia
    M Ballmaier
    Department of Pediatric Hematology and Oncology, Medizinische Hochschule Hannover, Germany
    Blood 97:139-46. 2001
    ..Flow cytometric analysis revealed absent surface expression of the TPO receptor c-Mpl in 3 of 3 patients...
  10. pmc Mpl Baltimore: a thrombopoietin receptor polymorphism associated with thrombocytosis
    Alison R Moliterno
    Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 101:11444-7. 2004
    ..We have reported defective thrombopoietin receptor (Mpl) protein expression in MPD patients...
  11. ncbi MPL mutations in 23 patients suffering from congenital amegakaryocytic thrombocytopenia: the type of mutation predicts the course of the disease
    Manuela Germeshausen
    Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
    Hum Mutat 27:296. 2006
    ..Mutations in the gene for the thrombopoietin receptor MPL were defined as the molecular cause in CAMT patients...
  12. pmc MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia
    Yana Pikman
    Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS Med 3:e270. 2006
    ..a consequence of activating mutations in certain hematopoietic-specific cytokine receptors, including the erythropoietin receptor (EPOR), the thrombopoietin receptor (MPL), or the granulocyte-colony stimulating factor receptor (GCSFR).
  13. ncbi Haematopoietic cell lineage distribution of MPLW515L/K mutations in patients with idiopathic myelofibrosis
    Wen Yang Hu
    Br J Haematol 137:378-9. 2007
  14. ncbi Anaemia characterises patients with myelofibrosis harbouring Mpl mutation
    Paola Guglielmelli
    Department of Haematology, University of Florence, Florence, Italy
    Br J Haematol 137:244-7. 2007
    The clinical and haematological phenotype of patients with myelofibrosis harbouring MPL(W515L/K) mutation has not been thoroughly investigated. Of 217 myelofibrosis subjects, 18 (8...
  15. ncbi Demonstration of MPLW515K, but not JAK2V617F, in in vitro expanded CD4+ T lymphocytes
    A Pardanani
    Leukemia 21:2206-7. 2007
  16. ncbi Evidence for MPL W515L/K mutations in hematopoietic stem cells in primitive myelofibrosis
    Ronan Chaligne
    Institut National de la Sante et de la Recherche Medicale INSERM, U790, Universite Paris XI, Institut Gustave Roussy, Villejuif, France
    Blood 110:3735-43. 2007
    The MPL (W515L and W515K) mutations have been detected in granulocytes of patients suffering from certain types of primitive myelofibrosis (PMF)...
  17. doi The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis: a report on 241 cases
    Jean Jacques Kiladjian
    Assistance Publique Hopitaux de Paris, Hopital Avicenne, Service d Hematologie Clinique, and Université Paris 13, Bobigny, France
    Blood 111:4922-9. 2008
    ..Underlying MPD is associated with severe forms of BCS, but current therapy appears to offset deleterious effects of MPD on the medium-term outcome...
  18. doi JAK and MPL mutations in myeloid malignancies
    Ayalew Tefferi
    Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
    Leuk Lymphoma 49:388-97. 2008
    ..JAK3 is important in lymphoid and JAK2 in myeloid cell proliferation and differentiation. The thrombopoietin receptor MPL is one of several JAK2 cognate receptors and is essential for myelopoiesis in general and ..
  19. doi Functional analysis of single amino-acid mutations in the thrombopoietin-receptor Mpl underlying congenital amegakaryocytic thrombocytopenia
    Marloes R Tijssen
    Department of Experimental Immunohaematology, Sanquin Research, Amsterdam, The Netherlands
    Br J Haematol 141:808-13. 2008
    ..Genetic defects in the gene encoding the thrombopoietin (Tpo) receptor, MPL, are the cause of this disease...
  20. doi Characteristics and clinical correlates of MPL 515W>L/K mutation in essential thrombocythemia
    Alessandro M Vannucchi
    Unita Funzionale di Ematologia, Dipartimento di Area Critica Medico Chirurgica, Universita degli Studi, Florence, Italy
    Blood 112:844-7. 2008
    ..MPLW515L/K patients presented lower hemoglobin levels and higher platelet counts than did wild type (wt) MPL; these differences were highly significant compared with MPLwt/JAK2V617F-positive patients...
  21. doi JAK2 and MPL mutations in myeloproliferative neoplasms: discovery and science
    O Kilpivaara
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Leukemia 22:1813-7. 2008
    ..MPN, genomic studies have identified JAK2 exon 12 mutations in JAK2V617F-negative PV and activating mutations in MPL in patients with JAK2V617F-negative ET and PMF...
  22. doi MPLW515L mutation in acute megakaryoblastic leukaemia
    K Hussein
    Institute of Pathology, Hannover Medical School, Hannover, Germany
    Leukemia 23:852-5. 2009
    The thrombopoietin receptor gene (MPL) is expressed in megakaryocytes and exhibits the gain of function point mutation W515K/L in approximately 5% of patients with primary myelofibrosis/idiopathic myelofibrosis (PMF) representing one ..
  23. doi The Asn505 mutation of the c-MPL gene, which causes familial essential thrombocythemia, induces autonomous homodimerization of the c-Mpl protein due to strong amino acid polarity
    Jianmin Ding
    Department of Medical Oncology and Immunology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
    Blood 114:3325-8. 2009
    ..activating mutation (Asn505) in the transmembrane domain (TMD) of c-MPL, which encodes the thrombopoietin receptor, caused familial essential thrombocythemia...
  24. pmc Evidence for a founder effect of the MPL-S505N mutation in eight Italian pedigrees with hereditary thrombocythemia
    Kun Liu
    Department of Biomedicine, Experimental Hematology, Basel University Hospital, Hebelstrasse 20, 4031 Basel, Switzerland
    Haematologica 94:1368-74. 2009
    ..Germ line mutations have been identified in the genes for thrombopoietin (THPO) and its receptor, MPL. A clustering of familial cases with the MPL-G1073A mutation that results in a serine to asparagine substitution (..
  25. pmc Hereditary thrombocytosis caused by MPLSer505Asn is associated with a high thrombotic risk, splenomegaly and progression to bone marrow fibrosis
    Luciana Teofili
    Department of Hematology, Catholic University, Rome, Italy
    Haematologica 95:65-70. 2010
    Background The MPL(Ser505Asn) mutation has been reported to be a cause of hereditary thrombocythemia...
  26. doi Induction of myeloproliferative disorder and myelofibrosis by thrombopoietin receptor W515 mutants is mediated by cytosolic tyrosine 112 of the receptor
    Christian Pecquet
    Ludwig Institute for Cancer Research, Brussels, Belgium
    Blood 115:1037-48. 2010
    Constitutively active JAK2V617F and thrombopoietin receptor (TpoR) W515L/K mutants are major determinants of human myeloproliferative neoplasms (MPNs)...
  27. doi CAMT in a female with developmental delay, facial malformations and central nervous system anomalies
    Nazareth Martinón-Torres
    Pediatric Hematology and Oncology Unit, Hospital Clinico Universitario de Santiago de Compostela, Spain
    Pediatr Blood Cancer 56:452-3. 2011
    ..It is caused by mutations in the thrombopoietin receptor gene, c-mpl, involved in the proliferation and differentiation of megakaryocytes and platelets...
  28. pmc Thrombopoietin receptor activation: transmembrane helix dimerization, rotation, and allosteric modulation
    Erin E Matthews
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520 8114, USA
    FASEB J 25:2234-44. 2011
    ..rotational variations in transmembrane (TM) helix interactions participate in the activity states of the thrombopoietin receptor (TpoR), a type 1 cytokine receptor that controls the production of blood platelets...
  29. pmc Effects of clinically relevant MPL mutations in the transmembrane domain revealed at the atomic level through computational modeling
    Tai Sung Lee
    BioMaPS Institute, Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey, United States of America
    PLoS ONE 6:e23396. 2011
    Mutations in the thrombopoietin receptor (MPL) may activate relevant pathways and lead to chronic myeloproliferative neoplasms (MPNs). The mechanisms of MPL activation remain elusive because of a lack of experimental structures...
  30. doi Congenital amegakaryocytic thrombocytopenia: clinical presentation, diagnosis, and treatment
    Matthias Ballmaier
    Department of Pediatric Hematology and Oncology Molecular Hematopoiesis, Hannover Medical School, Hannover, Germany
    Semin Thromb Hemost 37:673-81. 2011
    ..In most of the cases the disease is caused by homozygous or compound heterozygous mutations in the gene MPL encoding the receptor for the hematopoietic growth factor thrombopoietin...
  31. ncbi Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin
    Jianmin Ding
    Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Science, 1 Kawasumi, Mizuho cho, Mizuho ku, Nagoya 467 8601, Japan
    Blood 103:4198-200. 2004
    ..point mutation, serine 505 to asparagine 505 (Ser505Asn), was identified in the transmembrane domain of the c-MPL gene in all of the 8 members with thrombocythemia, but in none of the other 8 unaffected members in this FET family...
  32. ncbi MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients
    Animesh D Pardanani
    Division of Hematology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
    Blood 108:3472-6. 2006
    Recently, a gain-of-function MPL mutation, MPLW515L, was described in patients with JAK2V617F-negative myelofibrosis with myeloid metaplasia (MMM)...
  33. pmc Phenotypic variations and new mutations in JAK2 V617F-negative polycythemia vera, erythrocytosis, and idiopathic myelofibrosis
    Donna M Williams
    Johns Hopkins University School of Medicine, Baltimore, MD21205, USA
    Exp Hematol 35:1641-6. 2007
    ..IMF), are characterized by a spectrum of clinical features and linked by common genetic lesions in JAK2 and MPL. However, the clinical phenotypes in genetically undefined MPD patients are similar to those patients with JAK2 and ..
  34. doi MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort
    Philip A Beer
    Department of Haematology, University of Cambridge, Cambridge, United Kingdom
    Blood 112:141-9. 2008
    Activating mutations of MPL exon 10 have been described in a minority of patients with idiopathic myelofibrosis (IMF) or essential thrombocythemia (ET), but their prevalence and clinical significance are unclear...
  35. doi New mutations of MPL in primitive myelofibrosis: only the MPL W515 mutations promote a G1/S-phase transition
    R Chaligne
    INSERM, U790, Villejuif, France
    Leukemia 22:1557-66. 2008
    MPL (or thrombopoietin receptor, TPO-R) 515 mutations have recently been described in 5-10% of primitive myelofibrosis (PMF) cases as decisive oncogenic events capable of triggering the disease...
  36. doi Familial thrombocytosis caused by the novel germ-line mutation p.Pro106Leu in the MPL gene
    El Harith Abdelghaffar El-Harith
    Institute of Human Genetics, Medical University of Hannover, Hannover, Germany
    Br J Haematol 144:185-94. 2009
    ..germline mutations in the myeloproliferative leukaemia virus oncogene gene (MPL), which codes for the thrombopoietin receptor MPL...
  37. ncbi A novel MPL point mutation resulting in thrombopoietin-independent activation
    M Abe
    Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co Ltd, Tsukuba, Ibaraki, Japan
    Leukemia 16:1500-6. 2002
    Thrombopoietin (TPO) and its receptor (MPL) are important regulators of megakaryopoiesis. MPL belongs to a cytokine receptor superfamily...
  38. ncbi Effect of gravity change on the production of thrombopoietic growth factors
    A Fuse
    Dept Safty Res on Biologics, Natl Inst Infect Dis
    Biol Sci Space 15:302-3. 2001
    ..The cloning of the thrombopoietin (TPO), followed by the analysis of TPO and c-mpl (its cellular receptor) knockout mice confirmed its role as the primary regulator of thrombopoiesis...
  39. ncbi Thrombopoietin, but not cytokines binding to gp130 protein-coupled receptors, activates MAPKp42/44, AKT, and STAT proteins in normal human CD34+ cells, megakaryocytes, and platelets
    Marcin Majka
    Stem Cell Biology Program at James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA
    Exp Hematol 30:751-60. 2002
    The development of megakaryocytes is regulated by thrombopoietin (TPO), which binds to the c-mpl receptor, and by several other cytokines such as interleukin (IL)-6, IL-11, leukemia inhibitory factor (LIF), cilliary neurotropic factor (..
  40. ncbi 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
    I Vigon
    INSERM U363, ICGM, Hopital Cochin, Paris, France
    Oncogene 8:2607-15. 1993
    The v-mpl oncogene transduced in the myeloproliferative leukemia virus (MPLV) encodes a truncated form of a putative receptor protein that belongs to the cytokine receptor superfamily...
  41. ncbi Thrombopoietin and interleukin 11 have different modulatory effects on cell cycle and programmed cell death in primary acute myeloid leukemia cells
    A Tafuri
    Dipartimento di Biotecnologie Cellulari ed Ematologia, Universita La Sapienza di Roma, Rome, Italy
    Exp Hematol 27:1255-63. 1999
    The c-mpl ligand, thrombopoietin (TPO), is a physiologic regulator of platelet and megakaryocytic production, acting synergistically on thrombopoiesis with the growth factors interleukin 11 (IL-11), stem cell factor, interleukin 3 (IL-3),..
  42. ncbi p120c-cbl is present in human blood platelets and is differentially involved in signaling by thrombopoietin and thrombin
    A Oda
    Department of Internal Medicine, Keio University, Tokyo, Japan
    Blood 88:1330-8. 1996
    ..also induced tyrosine phosphorylation of p120c-cbl in FDCP cells genetically engineered to express the thrombopoietin receptor, c-Mpl...
  43. ncbi Monophosphoryl lipid A (MPL) as an adjuvant for anti-cancer vaccines: clinical results
    Christopher W Cluff
    GlaxoSmithKline Biologicals, 553 Old Corvallis Road, Hamilton, MT 59840, USA
    Adv Exp Med Biol 667:111-23. 2009
    ..developed and tested as monotherapeutics for the treatment of cancer, only 3-O-desacyl-4'-monophosphoryl lipid A (MPL) has been evaluated as a cancer vaccine adjuvant in published human clinical trials...
  44. doi Monophosphoryl lipid A (MPL) as an adjuvant for anti-cancer vaccines: clinical results
    Christopher W Cluff
    Glaxo Smith Kline Biologicals, 553 Old Corvallis Road, Hamilton, MT 59840, USA
    Adv Exp Med Biol 667:111-23. 2010
    ..and tested as monotherapeutics for the treatment of cancer,1-8 only 3-O-desacyl-4'-monophosphoryl lipid A (MPL) has been evaluated as a cancer vaccine adjuvant in published human clinical trials...
  45. doi Eltrombopag (75 mg) does not induce photosensitivity: results of a clinical pharmacology trial
    Carolyn J Bowen
    Oncology R and D Unit, GlaxoSmithKline, PO Box 13398, Research Triangle Park, NC 27709 3398, USA
    Photodermatol Photoimmunol Photomed 26:243-9. 2010
    Eltrombopag is an oral, small molecule, thrombopoietin receptor agonist approved in the United States for the treatment of chronic immune thrombocytopenic purpura and under investigation for treatment of thrombocytopenia due to other ..
  46. doi Romiplostim: a second-generation thrombopoietin agonist
    Claudia S Cohn
    Department of Pathology, NY Presbyterian Hospital, New York, NY, USA
    Drugs Today (Barc) 45:175-88. 2009
    ..TPO is a glycoprotein primarily produced in the liver. TPO, when binding to its receptor (c-Mpl), triggers a signaling cascade that leads to the differentiation and proliferation of megakaryocytes, with a ..
  47. ncbi Distribution and localization of monophosphoryl lipid A in selected tissues of the rat
    T S Reddy
    Xavier University of Louisiana, College of Pharmacy, New Orleans 70125, USA
    Immunopharmacol Immunotoxicol 18:145-59. 1996
    ..Rats were sacrificed 24h or 48h following intraperitoneal administration of MPL at a dose of 5mg/Kg. The presence of MPL in selected tissues was indicated by a positive reaction to MPL antibody...
  48. ncbi Forced GATA-1 expression in the murine myeloid cell line M1: induction of c-Mpl expression and megakaryocytic/erythroid differentiation
    Y Yamaguchi
    Department of Cell Differentiation, Kumamoto University School of Medicine, Japan
    Blood 91:450-7. 1998
    ..Because the c-mpl ligand, thrombopoietin, plays an important role in megakaryopoiesis, the expression of c-mpl and c-mpl ligand (..
  49. 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
    ..These studies are in contrast to results observed in vivo in mice deficient in the TPO or c-mpl gene (TPO-/- and c-mpl-/-)...
  50. ncbi High-level expression of Mpl in platelets and megakaryocytes is independent of thrombopoietin
    K Cohen-Solal
    INSERM U 362, Institut Gustave Roussy, Villejuif, France
    Blood 93:2859-66. 1999
    ..growth factor that regulates megakaryocytopoiesis and platelet production through binding to its receptor, Mpl, encoded by the c-mpl proto-oncogene...
  51. ncbi Signaling by the Mpl receptor involves IKK and NF-kappaB
    Ying Zhang
    Department of Biochemistry, Whitaker Cardiovascular Institute, Cancer Research Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    J Cell Biochem 85:523-35. 2002
    ..Here we report that activation of Mpl ligand is also linked to IKK and NF-kappaB activity...
  52. doi The effect of a novel, small non-peptidyl molecule butyzamide on human thrombopoietin receptor and megakaryopoiesis
    Wataru Nogami
    Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
    Haematologica 93:1495-504. 2008
    ..The aim of this study was to identify an orally bioavailable human Mpl activator that does not develop autoantibodies against endogenous thrombopoietin.
  53. ncbi Soluble thrombopoietin receptor (Mpl) and granulocyte colony-stimulating factor receptor directly stimulate proliferation of primitive hematopoietic progenitors of mice in synergy with steel factor or the ligand for Flt3/Flk2
    H Ku
    Department of Medicine, Medical University of South Carolina, Charleston, USA
    Blood 88:4124-31. 1996
    ..b>TPOR belongs to the cytokine receptor group that includes granulocyte colony-stimulating factor receptor (G-CSFR) and ..
  54. ncbi Clinical and prognostic significance of cytokine receptor expression in adult acute lymphoblastic leukemia: interleukin-2 receptor alpha-chain predicts a poor prognosis
    K Nakase
    Department of Hematology and Oncology, Mie University School of Medicine, Tsu, Japan
    Leukemia 21:326-32. 2007
    ..IL-3R, IL-4R, IL-5R, IL-6R, IL-7R, granulocyte-macrophage colony-stimulating factor R (GM-CSFR), G-CSFR, c-fms, c-mpl, c-kit and FLT3) in cells from 211 adults with acute lymphoblastic leukemia (ALL) by flow cytometry and determined ..
  55. ncbi A functional erythropoietin receptor is necessary for the action of thrombopoietin on erythroid cells lacking c-mpl
    Cecile Rouleau
    Laboratory for Cell and Molecular Biology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass 02215, USA
    Exp Hematol 32:140-8. 2004
    ..We hypothesized that thrombopoietin (TPO) exerts its mitogenic effects on erythroid cells, at least in part, via an interaction of TPO with the cells' erythropoietin receptor (EPO-R)...
  56. ncbi Tyrosine 462 of the membrane-proximal F'-G' loop of murine Mpl is not essential for high-affinity binding of thrombopoietin
    D F Sabath
    Department of Medicine, University of Washington, Seattle, WA 98195, USA
    Cytokine 12:127-33. 2000
    The ligand binding site of Mpl, the thrombopoietin (Tpo) receptor, has not been determined. Tyr(462)of murine Mpl corresponds to Tyr(421)of the common beta chain of the human IL-3, IL-5 and GM-CSF receptors...
  57. ncbi Interleukin-6 and interleukin-11 act synergistically with thrombopoietin and stem cell factor to modulate ex vivo expansion of human CD41+ and CD61+ megakaryocytic cells
    L Lazzari
    Milano Cord Blood Bank, Centro Trasfusionale e di Immunologia dei Trapianti, IRCCS Ospedale Maggiore, Via Francesco Sforza 35, 20122 Milan, Italy
    Haematologica 85:25-30. 2000
    Thrombopoietin (TPO), the ligand for the c-mpl receptor, regulates in vivo platelet production and increases the number of colony-forming unit megakaryocytes (CFU-MK)...
  58. ncbi Differentiation induced by the c-Mpl cytokine receptor is blocked by mutant Shc adaptor protein
    R J Hill
    Department of Hematology, SUGEN, Inc, Redwood City, California 94063, USA
    Cell Growth Differ 7:1125-34. 1996
    c-Mpl, a member of the cytokine receptor superfamily, induces both proliferative and differentiation responses when stimulated with its ligand thrombopoietin (TPO)...
  59. ncbi Deletion of the extracellular membrane-distal cytokine receptor homology module of Mpl results in constitutive cell growth and loss of thrombopoietin binding
    D F Sabath
    Department of Medicine, University of Washington, Seattle, WA 98195, USA
    Blood 94:365-7. 1999
    The thrombopoietin receptor, Mpl, is a member of the cytokine receptor superfamily. The extracellular domain of Mpl contains two copies of the cytokine receptor homology module (CRM)...
  60. pmc F104S c-Mpl responds to a transmembrane domain-binding thrombopoietin receptor agonist: proof of concept that selected receptor mutations in congenital amegakaryocytic thrombocytopenia can be stimulated with alternative thrombopoietic agents
    Norma E Fox
    Pediatric Hematology Oncology, University of California, San Diego, La Jolla, Calif 92017, USA
    Exp Hematol 38:384-91. 2010
    To determine whether specific c-Mpl mutations might respond to thrombopoietin receptor agonists.
  61. 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
    ..Through the application of gene targeting technology, the production of mice lacking TPO or its receptor c-Mpl has provided valuable insights into the physiological roles of TPO signalling...
  62. ncbi Promegapoietin, a family of chimeric growth factors, supports megakaryocyte development through activation of IL-3 and c-Mpl ligand signaling pathways
    P D Doshi
    Pharmacia Discovery Research, Chesterfield, MO 63198, USA
    Exp Hematol 29:1177-84. 2001
    The signaling pathways induced by promegapoietin (PMP), a family of chimeric growth factors that activate the human IL-3 and c-Mpl receptors, were investigated.
  63. ncbi Synergistic effects on erythropoiesis, thrombopoiesis, and stem cell competitiveness in mice deficient in thrombopoietin and steel factor receptors
    Jennifer Antonchuk
    Cancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia
    Blood 104:1306-13. 2004
    ..factor (SF) cytokine pathways in the regulation of hematopoiesis was investigated by generating mice lacking both c-Mpl and fully functional c-Kit receptors...
  64. ncbi Regulation of thrombopoietin levels by c-mpl-mediated binding to platelets
    P J Fielder
    Departments of Molecular Oncology, Genentech Inc, South San Francisco, CA USA
    Blood 87:2154-61. 1996
    The involvement of platelets and the c-mpl receptor in the regulation of thrombopoietin (TPO) plasma concentrations and tissue mRNA levels was investigated in both normal mice and mice defective in c-mpl (c-mpl-/-)...
  65. 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
    ..Addition of Mpl-ligand (Mpl-L; thrombopoietin) during the growth of EBs was found to mimic the effect of the MS-5 cell line on the ..
  66. ncbi Granulocyte-macrophage colony-stimulating factor is not responsible for residual thrombopoiesis in mpl null mice
    C L Scott
    The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia
    Exp Hematol 28:1001-7. 2000
    ..To examine the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in thrombopoiesis...
  67. ncbi Thrombopoietin alone or in the presence of stem cell factor supports the growth of KIT(CD117)low/ MPL(CD110)+ human mast cells from hematopoietic progenitor cells
    Arnold S Kirshenbaum
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1881, USA
    Exp Hematol 33:413-21. 2005
    ..We explored the ability of TPO alone or in the presence of stem cell factor (SCF) to support human mast cells (HuMCs)...
  68. ncbi Requirement for mitogen-activated protein kinase activation in the response of embryonic stem cell-derived hematopoietic cells to thrombopoietin in vitro
    Marie Dominique Filippi
    Institut National de la Sante et de la Recherche Medicale U362, Institut Gustave Roussy, Villejuif, France
    Blood 99:1174-82. 2002
    Enforced expression of c-mpl in embryonic stem (ES) cells inactivated for this gene results in protein expression in all the ES cell progeny, producing cells that do not belong to the megakaryocytic lineage and are responsive to PEG-..
  69. ncbi Autoantibody to c-Mpl (thrombopoietin receptor) in systemic lupus erythematosus: relationship to thrombocytopenia with megakaryocytic hypoplasia
    Masataka Kuwana
    Keio University School of Medicine, Tokyo, Japan
    Arthritis Rheum 46:2148-59. 2002
    To examine the prevalence, clinical associations, and pathogenic role of autoantibodies to c-Mpl, the thrombopoietin (TPO) receptor, in patients with systemic lupus erythematosus (SLE).
  70. ncbi Thrombopoietin as a drug: biologic expectations, clinical realities, and future directions
    Ibrahim C Haznedaroglu
    Department of Hematology, Hacettepe University Medical School, Ankara, Turkey
    Clin Appl Thromb Hemost 8:193-212. 2002
    After the cloning of thrombopoietin (c-mpl ligand, Tpo) in 1994, 2 recombinant thrombopoietic growth factors, full-length glycosylated recombinant human Tpo (reHuTPO) and polyethylene glycol conjugated megakaryocyte growth and ..
  71. ncbi Recombinant human thrombopoietin: basic biology and evaluation of clinical studies
    David J Kuter
    Hematology Oncology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Blood 100:3457-69. 2002
    ..Thrombopoietin (TPO), the c-Mpl ligand, is the primary physiologic regulator of megakaryocyte and platelet development...
  72. ncbi A rational chemical intervention strategy to circumvent bioactivation liabilities associated with a nonpeptidyl thrombopoietin receptor agonist containing a 2-amino-4-arylthiazole motif
    Amit S Kalgutkar
    Pharmacokinetics, Dynamics and Metabolism Department, Pfizer Global Research and Development, Groton, Connecticut 06340, USA
    Chem Res Toxicol 20:1954-65. 2007
    The current study examined the bioactivation potential of a nonpeptidyl thrombopoietin receptor agonist, 1-(3-chloro-5-((4-(4-fluoro-3-(trifluoromethyl)phenyl)thiazol-2-yl)carbamoyl)pyridine-2-yl)piperidine-4-carboxylic acid (1), ..
  73. doi Eltrombopag, an oral thrombopoietin receptor agonist, has no impact on the pharmacokinetic profile of probe drugs for cytochrome P450 isoenzymes CYP3A4, CYP1A2, CYP2C9 and CYP2C19 in healthy men: a cocktail analysis
    Julian Jenkins
    Oncology Medicine Development Center, GlaxoSmithKline Research and Development, Collegeville, PA 19426, USA
    Eur J Clin Pharmacol 66:67-76. 2010
    It is likely that the thrombopoietin receptor agonist eltrombopag will be administered concomitantly with other medications in the treatment of thrombocytopenia...
  74. doi Inflammation stimulates thrombopoietin (Tpo) expression in rat brain-derived microvascular endothelial cells, but suppresses Tpo in astrocytes and microglia
    Juan Zhang
    Department of Neonatology, Charite Universitatsmedizin Berlin, Berlin, Germany
    J Interferon Cytokine Res 30:465-9. 2010
    Thrombopoietin (Tpo) and its receptor (c-Mpl; TpoR), which primary regulate megakaryopoiesis and platelet production, are also expressed in the central nervous system (CNS)...
  75. 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...
  76. doi Eltrombopag: a novel oral thrombopoietin receptor agonist
    Shelby L Corman
    School of Pharmacy, University of Pittsburgh, Drug Information, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA
    Ann Pharmacother 44:1072-9. 2010
    ....
  77. ncbi Thrombopoietin: accumulating evidence for an important biological effect on the hematopoietic stem cell
    Kenneth Kaushansky
    Department of Medicine, University of California, San Diego, San Diego, California 92103, USA
    Ann N Y Acad Sci 996:39-43. 2003
    ..of erythroid, myeloid, and megakaryocytic progenitor cells and its genetic elimination or that of its receptor (c-mpl) reduces the numbers of these cells; all hematopoietic stem cells (HSCs) are c-mpl+; genetic elimination of c-mpl ..
  78. pmc Role of CD80 and CD86 in host immune responses to the recombinant hemagglutinin domain of Porphyromonas gingivalis gingipain and in the adjuvanticity of cholera toxin B and monophosphoryl lipid A
    Ping Zhang
    Department of Pediatric Dentistry, University of Alabama at Birmingham, 845 19th Street South, BBRB258 5, Birmingham, AL 35294 2170, USA
    Vaccine 25:6201-10. 2007
    ..investigated the effect of the mucosal adjuvants the B subunit of cholera toxin (CTB) and monophosphoryl lipid A (MPL) on the functional role of the costimulatory molecules for the induction of systemic and mucosal responses to Kgp-..
  79. ncbi Thrombopoietin in thrombocytopenias of childhood
    C Dame
    Department of Pediatrics, University of Florida College of Medicine, Gainesville 32610 0296, USA
    Semin Thromb Hemost 27:215-28. 2001
    This review summarizes the biology of thrombopoietin (TPO) in childhood. Studies on TPO and its receptor (c-mpl) have improved the understanding of inherited and acquired thrombocytopenias in childhood...
  80. pmc Signals emanating from the membrane proximal region of the thrombopoietin receptor (mpl) support hematopoietic stem cell self-renewal
    Wei Tong
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts, USA
    Exp Hematol 35:1447-55. 2007
    Studies using thrombopoietin -/- (TPO(-/-)) or TPO receptor, mpl(-/-) mice have established a critical role for TPO/mpl signaling in hematopoietic stem cell (HSC) development...
  81. ncbi Expression of c-mpl mRNA, the receptor for thrombopoietin, in acute myeloid leukemia blasts identifies a group of patients with poor response to intensive chemotherapy
    M Wetzler
    Department of Hematologic Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    J Clin Oncol 15:2262-8. 1997
    c-mpl, the human homolog of v-mpl, is the receptor for thrombopoietin...
  82. ncbi The mpl ligand: molecular and cellular biology of the critical regulator of megakaryocyte development
    K Kaushansky
    Division of Hematology, University of Washington School of Medicine, Seattle
    Stem Cells 12:91-6; discussion 96-7. 1994
    ..Recently, characterization of the proto-oncogene c-mpl revealed structural homology with the hematopoietic cytokine receptor family...
  83. 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...
  84. ncbi Surrogate thrombopoietin
    M Abe
    Institute for Drug Discovery Research, Yamanouchi Pharmaceutical, Tsukuba, Ibaraki, Japan
    Immunol Lett 61:73-8. 1998
    The extracellular domain of human c-Mpl, the receptor for thrombopoietin (TPO), was expressed as a chimeric protein with the interleukin-2 receptor alpha chain on the surface of murine B cell-line B300-19...
  85. pmc Role of the distal half of the c-Mpl intracellular domain in control of platelet production by thrombopoietin in vivo
    S M Luoh
    Department of Molecular Oncology, Genentech, Inc, South San Francisco, California 94080, USA
    Mol Cell Biol 20:507-15. 2000
    ..TPO exerts its effect through activation of the c-Mpl receptor and of multiple downstream signal transduction pathways...
  86. ncbi Differential role of Stat5 isoforms in effecting hematopoietic recovery induced by Mpl-ligand in lethally myelosuppressed mice
    Tamara I Pestina
    Division of Experimental Hematology, Department of Hematology Oncology, St Jude Children s Research Hospital, 332 N Lauderdale, Memphis, TN 38105 2794, USA
    Exp Hematol 31:1198-205. 2003
    To determine the role of the c-terminal half of c-Mpl in Mpl-L-induced myeloprotection and the importance of Stat5 isoforms in the survival signaling pathways induced by Mpl ligand.
  87. ncbi Normal thrombopoietin and its receptor (c-mpl) genes in children with essential thrombocythemia
    M L Randi
    Department of Medical and Surgical Sciences, University of Padua Medical School, Padua, Italy
    Pediatr Blood Cancer 44:47-50. 2005
    ..abnormalities as the cause of familiar cases of thrombocythemia similar derangements of TPO and/or its receptor (c-mpl) might be surmised to be at the root of increased platelet count also in non-familiar (sporadic) cases...
  88. 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
    ..of thrombopoietin (TPO) functioning to activate megakaryocyte differentiation and platelet release through the c-mpl receptor...
  89. ncbi Circulating thrombopoietin as an in vivo growth factor for blast cells in acute myeloid leukemia
    Francis Corazza
    Laboratory of Hematology, CHU Brugmann, 4 Place Van Gehuchten, B 1020 Brussels, Belgium
    Blood 107:2525-30. 2006
    ..TPO), the major growth factor for cells of the megakaryocytic lineage, is removed from circulation by binding to c-mpl receptors present on platelets and megakaryocytes...
  90. ncbi A preliminary investigation into the action of anagrelide: thrombopoietin-c-Mpl receptor interactions
    John M McCarty
    Department of Hematology Oncology and Bone Marrow Transplantation Program, Massey Cancer Center, VCU Health Systems MCV Hospitals at Virginia Commonwealth University, Richmond, 23298, USA
    Exp Hematol 34:87-96. 2006
    ..Using CD34(+) stem cells and murine BaF3 cells transfected with the human or murine TPO receptor, c-Mpl (BaF3mpl), the effect of anagrelide on cell differentiation, proliferation, and signaling was examined in the ..
  91. doi Impact of chicken thrombopoietin and its receptor c-Mpl on hematopoietic cell development
    Petr Bartunek
    Institute of Molecular Genetics, Prague, Czech Republic
    Exp Hematol 36:495-505. 2008
    The primary objective of this study was to identify and clone the first nonmammalian thrombopoietin (TPO), chicken TPO, and its receptor c-Mpl for the purpose of characterizing their activities both in vitro and in vivo.
  92. doi hNUDC promotes the cell proliferation and differentiation in a leukemic cell line via activation of the thrombopoietin receptor (Mpl)
    Y S Tang
    State Key Laboratory of Biocontrol and The Key Laboratory of Gene Engineering of Education Ministry, Zhongshan University, Guangzhou, People s Republic of China
    Leukemia 22:1018-25. 2008
    ..of a fungal nuclear migration protein (hNUDC) that binds specifically with the extracellular domain of thrombopoietin receptor (Mpl)...
  93. doi Comparative analyses of the small molecule thrombopoietin receptor agonist eltrombopag and thrombopoietin on in vitro platelet function
    Joseph A Erhardt
    Department of Oncology, GlaxoSmithKline, Collegeville, PA 19426, USA
    Exp Hematol 37:1030-7. 2009
    The thrombopoietin receptor (TPOR) is a therapeutic target for treatment of thrombocytopenia because stimulation of this receptor results in enhanced megakaryocyte proliferation, differentiation, and ultimately platelet production...
  94. ncbi Single administration of thrombopoietin to lethally irradiated mice prevents infectious and thrombotic events leading to mortality
    M A Mouthon
    Institut de Protection et de Surete Nucleaire, IPSN, Fontenay aux Roses Cedex, France
    Exp Hematol 29:30-40. 2001
    A sufficiently high dose of thrombopoietin to overcome initial c-mpl-mediated clearance stimulates hematopoietic reconstitution following myelosuppressive treatment...
  95. doi Thrombopoietin is a growth factor for rat hepatic progenitors
    Eva Schmelzer
    Department of Cell Culture and Stem Cell Biology, Biomedical Biotechnical Center, University of Leipzig, Leipzig, Germany
    Eur J Gastroenterol Hepatol 20:209-16. 2008
    ..Therefore, the influence of TPO on the proliferation of fetal hepatic progenitors in vitro compared with that of adult hepatocytes was analyzed. The expression of the TPO receptor, c-mpl, was investigated in fetal and adult liver.
  96. ncbi Analysis of a monophosphoryl lipid A immunostimulant preparation from Salmonella minnesota R595 by high-performance liquid chromatography
    S R Hagen
    Ribi ImmunoChem Research, Inc, Hamilton, MT 59840, USA
    J Chromatogr A 767:53-61. 1997
    b>MPL immunostimulant, a 4'-monophosphoryl lipid A (MLA) preparation obtained from the lipopolysaccharide of Salmonella minnesota R595, is being developed for several clinical indications...
  97. ncbi Combined inhibition effects of tacrolimus and methylprednisolone on in vitro human lymphocyte proliferation
    M J Lee
    Department of Pharmaceutics, State University of New York at Buffalo 14260, USA
    Immunopharmacol Immunotoxicol 17:335-45. 1995
    ..We investigated the influence of combinations of FK 506 and methylprednisolone (MPL) on the suppression of in vitro human lymphocyte proliferation...
  98. ncbi A Th1-inducing adjuvant, MPL, enhances antibody profiles in experimental animals suggesting it has the potential to improve the efficacy of allergy vaccines
    A W Wheeler
    Allergy Therapeutics Ltd, Worthing, UK
    Int Arch Allergy Immunol 126:135-9. 2001
    Monophosphoryl lipid A (MPL) is a detoxified derivative of the lipopolysaccharide (LPS) moiety of Salmonella minnesota R595, which has retained immunostimulatory activities...
  99. ncbi Clinical trials of prophylactic and therapeutic herpes simplex virus vaccines
    Lawrence R Stanberry
    The Sealy Center for Vaccine Development, The University of Texas Medical Branch, Galveston, Texas 77555 0351, USA
    Herpes 11:161A-169A. 2004
    ..The Chiron gD2gB2-MF59 vaccine gave transient protection of less than 6 months. The GlaxoSmithKline gD2-alum MPL vaccine conferred a 73-74% reduction in acquisition of symptomatic HSV-2 disease and a 38-42% reduction in the ..

Research Grants65

  1. MOLECULAR AND CELLULAR BIOLOGY OF THROMBOPOIETIN
    Kenneth Kaushansky; Fiscal Year: 2013
    ..Through its interaction with the c-Mpl receptor, TPO initiates a signaling cascade by triggering the phosphorylation and activation of Jak2...
  2. Functional Studies of the Extracellular Domain of Mpl
    DANIEL SABATH; Fiscal Year: 2004
    ..This proposal is designed to study the structure/function relationships of Mpl, the thrombopoietin receptor, in ligand binding and in control of receptor activation...
  3. Mechanism of Lnk function in cytokine receptor signaling
    Wei Tong; Fiscal Year: 2009
    ..The adaptor protein Lnk negatively regulates signaling transduction of the Epo receptor (EpoR) and Tpo receptor (mpl), thereby downregulating Tpo-mediated megakaryocytopoiesis and Epo-mediated erythropoiesis...
  4. THROMBOPOIETIN SIGNAL TRANSDUCTION
    Jonathan Drachman; Fiscal Year: 2000
    ..The c-Mpl proto-oncogene, an orphan cytokine receptor, became the focus of intense investigation after it was shown that it ..
  5. REGULATION OF HEMATOPOIESIS BY THROMBOPOIETIN
    Warren Alexander; Fiscal Year: 2001
    ..The thrombocytopenia in mice lacking TPO or its receptor c-Mpl is evidence that TPO is the dominant physiologic regulator of megakaryocytopoiesis, but that sufficient TPO-..
  6. Inhibition of Histone Deacetylase in Myeloproliferative Neoplasms
    Golam Mohi; Fiscal Year: 2012
    ..Additional mutations in the thrombopoietin receptor MPL (MPLW515L, MPLW515K) have been found in 5-10% cases of ET and PMF...
  7. Wei Tong; Fiscal Year: 2014
    ..The overall goal of this project is to examine the respective contributions of Wnt, mTOR, and Tpo/Mpl/JAK2 signaling in the response to GSK-3 inhibition and to define the role of GSK-3 in regulating these pathways ..
  8. Erythropoietin Blockade for the Treatment of Cancer
    C Anthony Blau; Fiscal Year: 2012
    ..Ectopic expression of a modified derivative of the thrombopoietin receptor (F36VMpl) in hematopoietic stem cells and their progeny allows for CID-dependent blood cell production, ..
  9. Glen D Raffel; Fiscal Year: 2016
    ..Preliminary data shows Ott1 interacts with a region of the c-Mpl gene involved in alternative splicing...
  10. Wei Tong; Fiscal Year: 2016
    ..One important signaling axis for HSC biology is thrombopoietin (TPO) and its receptor Mpl, signaling through Janus Kinase (JAK2). TPO-/- or Mpl-/- mice show diminished HSC self-renewal...
  11. Melissa A Kacena; Fiscal Year: 2016
    ..Second, TPO more rapidly restores bone contour at the fracture site by binding to c-mpl on osteoclast (OC) progenitors, increasing osteoclastogenesis, and subsequently coupled remodeling...
  12. SIGNAL TRANDUCTION IN POLYCYTHEMIA VERA
    Jerry Spivak; Fiscal Year: 1999
    ..to date, we now plan to examine TPO-mediated PV platelet signal transduction with respect to platelet c-Mpl expression, the interaction of c-Mpl in PV megakaryocytes as compared to PV platelets...
  13. MOLECULAR PHYSIOLOGY OF THROMBOPOIETIN
    David Kuter; Fiscal Year: 1999
    ..Using cultures of megakaryocyte precursor cells efforts will also be made to determine how the thrombopoietin receptor is itself regulated...
  14. C-MPL AND EARLY HUMAN HEMATOPOIESIS
    William Kerr; Fiscal Year: 2003
    Thrombopoietin (TPO) via its receptor, c-mpl, is the primary physiological regulatory of platelet production...
  15. CONDITIONAL ACTIVATION OF MPL AS A GENE THERAPY STRATEGY
    Robert Richard; Fiscal Year: 2006
    ..that express a fusion protein containing a CID binding domain linked to the intracellular portion of the thrombopoietin receptor, mpl...
  16. Mpl: Signal Trafficking and Megakaryocytopoiesis
    DEBRA DAHLEN; Fiscal Year: 2003
    ..to gain insight into the signal transduction mechanisms of the growth factor thrombopoietin (TPO) and its receptor, Mpl, and to provide in-depth training in molecular biology for Dr. Debra Dahlen...
  17. Therapeutic Synergy of Membrane-Anchored Cytokines, TLR Ligands &Ukrain
    Erica Bozeman; Fiscal Year: 2012
    ..cells of the adaptive immune response, the simultaneous vaccination with the TLR- ligands, monophosphoryl lipid A (MPL) and unmethylated CpG-motifs (CpG), will activate innate immune cells, most notably DCs that will further augment ..
  18. Robert K Ernst; Fiscal Year: 2014
    ..Recently, the lipid A mimetic (monophosphoryl lipid A, MPL) adjuvant has been combined with alum (AS04) in two FDA-approved vaccines (Cervarix (Human Papilloma Virus), and ..
  19. Xinyuan Chen; Fiscal Year: 2014
    ..A laser-based powder delivery (LPD) in combination with a clinical monophosphoryl lipid A (MPL) adjuvant (MPL/LPD) is proposed for improved newborn immunization...
  20. The Role of TLR4 and RSV F Protein in Immunity to RSV
    JORGE C BLANCO; Fiscal Year: 2013
    ..used in the failed trials, newly formulated with a non-toxic adjuvant and TLR4 agonist, monophosphoryl lipid A (MPL), suppressed FI-RSV vaccine-enhanced disease by blunting the mixed Th1- and Th2-type "cytokine storm" that is ..
  21. Developing Immunotherapeutics for Methamphetamine Abuse
    THOMAS RICHARD KOSTEN; Fiscal Year: 2010
    ..These adjuvants include CpG oligonucleotides, MPL, and a squalene-based adjuvant;CFA and alum will be included as controls...
  22. Ross L Levine; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): Activating mutations in JAK2 and in MPL are present in the majority of patients with the myeloproliferative neoplasms (MPN) essential thrombocytosis (ET) and primary myelofibrosis (PMF)...
  23. LEE MARK WETZLER; Fiscal Year: 2016
    ..inflammasomes mediated immune activation, other TLR ligands, including CpG DNA (TLR9), and monophosphoryl lipid A (MPL)(TLR4), and QS-21...
  24. Mechanisms of Monophosporyl Lipid A Immuno-Modulation in Septic Shock
    CHRISTOPHER DAVID MICHAEL ROMERO; Fiscal Year: 2010
    ..Greater mechanistic understanding is needed for MPL and other immunomoduolators to become clinically available treatment options...
  25. Xinyuan Chen; Fiscal Year: 2014
    ..Encapsulation of nicotine vaccine and a safe cutaneous monophosphoryl lipid A (MPL) adjuvant into mixed poly(D,L-lactic-co-glycolic acid) (PLGA) particles with different sizes is expected to ..
  26. John D Crispino; Fiscal Year: 2016
    ..However, upon acquisition of mutations in key signaling molecules, such as MPL or JAK2, megakaryocyte progenitors expand and lead to thrombocytosis in ET or myelofibrosis in PMF...
  27. Lynn Soong; Fiscal Year: 2014
    ..regimens, in conjunction with novel TLR4- adjuvants glucopyranosyl lipid A (GLA) and monophosphoryl lipid A (MPL)...
  28. REGULATION OF IMMUNE RESPONSE IN THE ORAL CAVITY
    Suzanne Michalek; Fiscal Year: 2003
    ..The adjuvants to be used are the B subunit of cholera toxin (rCTB) and monophosphoryl lipid A (MPL). Adult volunteers will be used in this aspect of the study...
  29. DEVELOP AND EVALUATE NEW LEPROSY AND TB VACCINES
    Thomas Gillis; Fiscal Year: 2003
    ..MT, 3) MT culture filtrate in adjuvant prepared from the nontoxic derivative of lipid A from Salmonella minnesota (MPL, [plus IL-2]) and 4) pooled MT genomic vaccine, (3) test protective efficacy, potency and immunotherapeutic ..
  30. PROLIFERATIVE SWITCH FOR GENETICALLY MODIFIED CELLS
    C Anthony Blau; Fiscal Year: 2004
    ..We have achieved that goal. Our approach uses a derivative of the thrombopoietin receptor (mpl) that delivers a conditional growth signal in response to a drug called a chemical inducer of ..
  31. CHRONIC HYPOXIA AND RESISTANCE TO MYOCARDIAL ISCHEMIA
    John E Baker; Fiscal Year: 2010
    ..Tpo) is the primary physiologic regulator of megakaryocyte and platelet development through the Tpo receptor mpl. Recently we have made the novel and serendipitous observation that Tpo is an extraordinarily potent ..
  32. Development of a Novel Vaccine Against Herpes Simplex Type 2
    DEBORAH SPECTOR; Fiscal Year: 2009
    ..generated by the optimal combination of conserved, essential HSV-2 genes and gD2 DNA will be compared to the gD2/MPL/alum protein subunit vaccine that was partially protective in clinical testing...
  33. Paraventricular nucleus regulatory mechanisms in stress and hypertension
    Colin Sumners; Fiscal Year: 2013
    ..indicate that MIF acts within PVN neurons of normotensive rats via its intrinsic thiol protein oxidoreductase (TPOR) activity to attenuate the cardiovascular actions of Ang II...
  34. Targeted Dendritic Cell Activation through Multi-Adjuvant Liposomes
    Gretchen Jimenez; Fiscal Year: 2013
    ..We have shown that the TLR4 agonist, MPL has an immunostimulatory effect and hypothesize that other TLR agonists and receptor-binding ligands will influence ..
  35. STEVEN GREGORY REED; Fiscal Year: 2016
    ..KSAC, together with the adjuvant formulation MPL-SE, provides partial protection against a needle challenge of L. infantum or L. donovani...
  36. John D Crispino; Fiscal Year: 2016
    ..in DS leukemia, this research is also relevant to other leukemias with acquired trisomy 21, such as hyperdiploid ALL and to myeloproliferative neoplasms, in particular the large group of ET and PMF cases that lack JAK2 or MPL mutations.
  37. Development of Efficacious and Stable Nasal Vaccine Formulations
    Herman F Staats; Fiscal Year: 2013
    ..MCAP combined with TLR ligands MPL or CpG provided adjuvant activity that was superior to any adjuvant used alone...
  38. HMGB1-Derived Peptides As Vaccine Adjuvants
    Bradley T Messmer; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Currently, aluminum compounds and more recently MPL are the only adjuvants approved by the FDA for use in humans in the U.S...
  39. Microfabricated 3D Environments for Characterizing Bacterial Group Behaviors
    Marvin Whiteley; Fiscal Year: 2010
    ..In these studies, a novel approach based on multiphoton lithography (MPL) will be developed for microfabricating defined, arbitrary topographies using biological building blocks (proteins) ..
  40. Antigenic variation by multiple promoter inversions in Mycoplasma penetrans
    Michael Calcutt; Fiscal Year: 2009
    ..discloses the presence of 50 lipoprotein genes, 38 of which constitute a large paralogous family (designated mpl) that includes the abundant lipoproteins P35 and P42...
  41. Liposomal Nicotine Vaccine Development
    Gary Fujii; Fiscal Year: 2011
    ..Our initial formulations will incorporate the following TLR agonists for testing: MPL (TLR4);loxoribine (TLR7/8) and;an oligonucleotide containing a CpG motif (TLR9)...
  42. ApoVax104-HPV as a Novel Vaccine for Cervical Cancer
    KATHRYN MACLEOD; Fiscal Year: 2009
    ..E749-57) was more effective than 3 benchmark adjuvants (lipopolysaccharide, (LPS), Monophosphoryl Lipid A (MPL), and CpG oligonucleotide (CpG), in the generation of primary and long- term T cell memory as well as in the ..
  43. Formulation of TLR 3, 7, and 8 Agonists in Conjugatable Adjuvant Lipid Vesicles
    SAMON HO; Fiscal Year: 2013
    ..We have already shown that the TLR4 agonist, MPL has an immunostimulatory effect and hypothesize that other TLR agonists will influence the immune response profile ..
  44. Leish-111f + MPL-SE vaccine development for treatment of cutaneous leishmaniasis
    FRANCO PIAZZA; Fiscal Year: 2006
    ..proposal for implementing a Phase 2 clinical trial to evaluate the safety and immunogenicity of the Leish-111 f + MPL-SE vaccine in the treatment of cutaneous leishmaniasis caused by Leishmania major in Tunisia...
  45. LISTERIA PHOSPHOLIPASE ACTIVATION & CELL-TO-CELL SPREAD
    HELENE MARQUIS; Fiscal Year: 2002
    ..biochemical evidence that the intracellular activation of pro PC-PLC is mediated by a bacterial metalloprotease (Mpl), which is also active in broth culture, and a cysteine protease, whose activity can only be detected during ..
  46. Christopher H Clegg; Fiscal Year: 2014
    ..There is a very strong rationale to develop GLA for allergy based on its superior drug profile to MPL, a related TLR4 agonist that accelerates desensitization in people...
  47. Mucosal RSV vaccine using CpG oligodeoxynucleotides
    Gregory Prince; Fiscal Year: 2003
    ..phenotype associated with vaccine-enhanced disease could be eliminated by the addition of monophosphoryl lipid A (MPL), and thus we believe that the atypical histopathology accompanying F/CpG immunization can also be eliminated ..
  48. MUROPEPTIDE RECYCLING PATHWAY & BETA LACTAMASE INDUCTION
    James Park; Fiscal Year: 2006
    ..Antigen 43 causes autoaggregation which facilitates biofilm formation. Deletion of either murein peptide ligase (mpl) or murein peptide amidase A (mpaA) results in production of tripeptide and antigen 43 suggesting that accumulation ..
  49. THE YEAST NUCLEAR PORE COMPLEX
    Michael Douglas; Fiscal Year: 1991
    ..Purification of a highly enriched yeast nuclear matrix pore lamina (MPL) fraction yields a protein profile with 12-15 proteins...
  50. Multi-drug Resistance Tuberculosis as Bioterrorism Agent
    Luis Cantarero; Fiscal Year: 2004
    ..This work will test vaccine candidates 72f, a recombinant polyprotein, and a mixture of low oxygen proteins both in MPL-SE adjuvant that have shown extremely promising early results by our consultants in mouse, guinea pig and monkey ..
  51. Listeria phospholipase C: sorting, activation, release
    HELENE MARQUIS; Fiscal Year: 2007
    ..A bacterial metalloprotease (Mpl) is involved in the regulation of PC-PLC activation and secretion...
  52. Novel Adjuvants/Delivery Systems for Biodefense Vaccines
    NICHOLAS VALIANTE; Fiscal Year: 2005
    ..This will be done by first formulating rPA with our existing delivery systems and synthetic MPL derivatives to evaluate the general performance of these novel formulations in immunogenicity/ protection studies (..
  53. PLACENTAL LACTOGENS--REGULATION AND BIOACTIVITY
    Frank Talamantes; Fiscal Year: 1999
    The mouse placenta produces two placental lactogens: mouse placental lactogen-I (mPL-I) and mPL-II...
  54. MOLECULAR BIOLOGY OF HEMOPOIETIC STEM CELLS
    George Stamatoyannopoulos; Fiscal Year: 2004
    ..They will characterize features of mpl of GCSF receptors that are involved in stem cell expansion and test whether transient activation of these receptors ..
  55. STRUCTURE/FUNCTION STUDIES OF MPL
    DIANA SABATH; Fiscal Year: 2000
    The overall objectives of this project are to gain insights into the role of the growth factor receptor, Mpl, in hematopoiesis and to provide in-depth training in Molecular Biology for Dr. Diana Sabath...
  56. Thrombopoietin Signaling: The Role of Src Kinases
    BRIAN LANNUTTI; Fiscal Year: 2007
    ..Understanding the signaling mechanisms of Mp1 and its interactions with other signaling molecules may lead to novel approaches in the treatment of a number of hematologic and other diseases. ..
  57. Role of c-Mpl in HIV-1 Induced Cytopenias
    PRASAD KOKA; Fiscal Year: 2008
    ..PI will focus this research investigation on the hematopoietic cytokine, thrombopoietin (Tpo) and its receptor (c-mpl) since they are important effectors of multilineage hematopoiesis...
  58. THE ROLE OF PL3K IN THROMBOPOIETIN SIGNALING
    Amy Geddis; Fiscal Year: 2005
    ..MK) development and plays an important role in hematopoiesis in general, but the mechanisms by which its receptor, Mpl, signals to stimulate cell survival and proliferation are incompletely understood...
  59. Immune Pathways as Prerequisites for Adjuvants' Efficacy
    George Hui; Fiscal Year: 2004
    ....
  60. GROWTH FACTORS IN NORMAL AND NEOPLASTIC HEMATOPOIESIS
    Kenneth Kaushansky; Fiscal Year: 2006
    ..efficiency of translation or 2) affect TPO blood levels indirectly by altering expression of the TPO receptor, c-mpl; B) determine the intramolecular pathways employed by TPO that transmit signals for MK survival, proliferation and ..
  61. Cell biology of megakaryocytes and platelets 2005
    Kenneth Kaushansky; Fiscal Year: 2005
    ..This application is a request for partial funds to support the attendance of speakers and discussion leaders, and selected postdoctoral fellows and students at this important new meeting. ..
  62. 2007 Cell Biology of Megakaryocytes and Platelets GRC
    Kenneth Kaushansky; Fiscal Year: 2007
    ..e. speakers, discussion leaders, postdoctoral fellows, students, etc.) at this important scientific meeting. [unreadable] [unreadable] [unreadable]..
  63. Molecular Pathogenesis of Polycythemia Vera
    ALISON MOLITERNO; Fiscal Year: 2008
    ..We previously identified unique molecular defects in thrombopoietin (TPO) receptor (Mpl) gene expression that were associated clinically with distinct myeloproliferative phenotypes...
  64. Clinical Applications of a Novel Fanconi Anemia Assay
    Akiko Shimamura; Fiscal Year: 2007
    ..abstract_text> ..
  65. Apoptosis in myelofibrosis with myeloid metaplasia
    Ruben Mesa; Fiscal Year: 2006
    ..abstract_text> ..