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The physiology of platelet production
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Kuter DJ: The physiology of platelet production. Stem Cells 1996, 14(suppl 1):88-101.
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Stem Cells
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Totowa: Humana
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Thrombopoiesis and Thrombopoietins: Molecular, Cellular, Preclinical and Clinical Biology. Edited by Kuter DJ, Hunt P, Sheridan W, Zucker-Franklin D. Totowa: Humana; 1997. This multiauthored book is a comprehensive review of all of the published and much unpublished data about the Mpl ligands. It reviews the history, discovery, structure, function, and preclinical studies of thrombopoietin.
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Thrombopoiesis and Thrombopoietins: Molecular, Cellular, Preclinical and Clinical Biology
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Kuter, D.J.1
Hunt, P.2
Sheridan, W.3
Zucker-Franklin, D.4
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3
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0028832719
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Point mutations within a dimer interface homology domain of c-Mpl induce constitutive receptor activity and tumorigenicity
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Alexander WS, Metcalf D, Dunn AR: Point mutations within a dimer interface homology domain of c-Mpl induce constitutive receptor activity and tumorigenicity. EMBO J 1995, 14:5569-5578.
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EMBO J
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Alexander, W.S.1
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0029963565
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Functional regions of the mouse thrombopoietin receptor cytoplasmic domain: Evidence for a critical region which is involved in differentiation and can be complemented by erythropoietin
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Porteu F, Rouyez M-C, Cocault L, Benit L, Charon M, Picard F, Gisselbrecht S, Souyri M, Dusanter-Fourt I: Functional regions of the mouse thrombopoietin receptor cytoplasmic domain: evidence for a critical region which is involved in differentiation and can be complemented by erythropoietin. Molec Cell Biol 1996, 16:2473-2482.
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Molec Cell Biol
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Porteu, F.1
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Benit, L.4
Charon, M.5
Picard, F.6
Gisselbrecht, S.7
Souyri, M.8
Dusanter-Fourt, I.9
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5
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0028935483
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Constitutive activation of a variant of the env-mpl oncogene product by disulfide-linked homodimerization
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Courtois G, Benit L, Mikaeloff Y, Pauchard M, Charon M, Varlet P, Gisselbrecht S: Constitutive activation of a variant of the env-mpl oncogene product by disulfide-linked homodimerization. J Virol 1995, 69:2794-2800.
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Courtois, G.1
Benit, L.2
Mikaeloff, Y.3
Pauchard, M.4
Charon, M.5
Varlet, P.6
Gisselbrecht, S.7
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6
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0029912139
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Effects of recombinant human megakaryocyte growth and development factor on platelet activation
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Montrucchio G, Brizzi MF, Calosso G, Marengo S, Pegoraro L, Camussi G: Effects of recombinant human megakaryocyte growth and development factor on platelet activation. Blood 1996, 87:2762-2768.
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Blood
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Montrucchio, G.1
Brizzi, M.F.2
Calosso, G.3
Marengo, S.4
Pegoraro, L.5
Camussi, G.6
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7
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0029943307
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Dose-response effects of pegylated megakaryocyte growth and development factor on platelet production and function in nonhuman primates
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Harker LA, Marzec UM, Hunt P, Kelly AB, Tomer A, Cheung E, Hanson SR, Stead RB: Dose-response effects of pegylated megakaryocyte growth and development factor on platelet production and function in nonhuman primates. Blood 1996, 88:511-521. This study provides a comprehensive study of the effects of PEG-MGDF on platelet number and function in baboons. Doses of PEG-MGDF ranging from 0.05 to 2.5 μg/kg/d were injected and the log-linear relationship of dose to response was demonstrated for megakaryocyte number, ploidy, size, and platelet concentration. Effects on platelet function were analyzed by aggregometry and by measuring platelet and fibrin deposition in blood vessels and Dacron vascular grafts.
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Blood
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Harker, L.A.1
Marzec, U.M.2
Hunt, P.3
Kelly, A.B.4
Tomer, A.5
Cheung, E.6
Hanson, S.R.7
Stead, R.B.8
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8
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0029080417
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Megakaryocyte growth and developmental factor (MGDF) moderately enhances in-vitro platelet aggregation
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Toombs CF, Young CH, Glaspy JA, Varnum BC: Megakaryocyte growth and developmental factor (MGDF) moderately enhances in-vitro platelet aggregation. Thromb Res 1995,80:23-33.
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Thromb Res
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Toombs, C.F.1
Young, C.H.2
Glaspy, J.A.3
Varnum, B.C.4
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9
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0029923645
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Relative reactivity of platelets from thrombopoietin- and interleukin-6-treated dogs
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Peng J, Friese P, Wolf RF, Harrison P, Downs T, Lok S, Dale GL, Burstein SA: Relative reactivity of platelets from thrombopoietin- and interleukin-6-treated dogs. Blood 1996, 87:4158-4163.
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Blood
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Peng, J.1
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Lok, S.6
Dale, G.L.7
Burstein, S.A.8
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10
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0030068687
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Regulation of platelet production and function by megakaryocyte growth and development factor in nonhuman primates
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Harker LA, Hunt P, Marzec UM, Kelly AB, Tomer A, Hanson SR, Stead RB: Regulation of platelet production and function by megakaryocyte growth and development factor in nonhuman primates. Blood 1996, 87:1833-1844. This enormous work complements Harker er al. (Blood 1996, 88:511-521) and describes the effects in baboons of the administration of PEG-MGDF at 5 μg/kg/d for 28 days. The course of the platelet count rise is documented as is the increase in bone marrow megakaryocyte number, volume, and ploidy. Platelet kinetic studies demonstrated a 6.5-fold increase in megakaryocyte mass. Platelet aggregation response to multiple agonists was enhanced in the first week but not subsequently. There was no increase in thrombi clinically.
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(1996)
Blood
, vol.87
, pp. 1833-1844
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Harker, L.A.1
Hunt, P.2
Marzec, U.M.3
Kelly, A.B.4
Tomer, A.5
Hanson, S.R.6
Stead, R.B.7
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11
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0029943307
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Harker LA, Hunt P, Marzec UM, Kelly AB, Tomer A, Hanson SR, Stead RB: Regulation of platelet production and function by megakaryocyte growth and development factor in nonhuman primates. Blood 1996, 87:1833-1844. This enormous work complements Harker er al. (Blood 1996, 88:511-521) and describes the effects in baboons of the administration of PEG-MGDF at 5 μg/kg/d for 28 days. The course of the platelet count rise is documented as is the increase in bone marrow megakaryocyte number, volume, and ploidy. Platelet kinetic studies demonstrated a 6.5-fold increase in megakaryocyte mass. Platelet aggregation response to multiple agonists was enhanced in the first week but not subsequently. There was no increase in thrombi clinically.
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(1996)
Blood
, vol.88
, pp. 511-521
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Harker1
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12
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0030052617
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Thrombopoietin induces tyrosine phosphorylation of Stat3 and Stat5 in human blood platelets
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Miyakawa Y, Oda A, Druker BJ, Miyazaki H, Handa M, Ohashi H, Ikeda Y: Thrombopoietin induces tyrosine phosphorylation of Stat3 and Stat5 in human blood platelets. Blood 1996, 87:439-446.
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Blood
, vol.87
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Miyakawa, Y.1
Oda, A.2
Druker, B.J.3
Miyazaki, H.4
Handa, M.5
Ohashi, H.6
Ikeda, Y.7
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13
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0028827190
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Thrombopoietin, C-Mpl ligand, induces tyrosine phosphorylation of Tyk2, JAK2, and STAT3, and enhances agonist-induced aggregation in platelets in vitro
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Ezumi Y, Takayama H, Okuma M: Thrombopoietin, C-Mpl ligand, induces tyrosine phosphorylation of Tyk2, JAK2, and STAT3, and enhances agonist-induced aggregation in platelets in vitro. FEB Letters 1995, 374:48-52.
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FEB Letters
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Ezumi, Y.1
Takayama, H.2
Okuma, M.3
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14
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0029865443
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Regulation of thrombopoietin levels by c-Mpl-mediated binding to platelets
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Fielder PJ, Gurney AL, Stefanich E, Marian M, Moore MW, Carver-Moore K, de Sauvage FJ: Regulation of thrombopoietin levels by c-Mpl-mediated binding to platelets. Blood 1996, 87:2154-2161. This elegant and comprehensive study measures the binding of radiolabelled recombinant thrombopoietin to normal and c-Mpl-deficient mice. These c-Mpl-deficient mice did not have increased hepatic thrombopoietin mRNA. Labelled thrombopoietin bound to platelets in vivo and in vitro was internalized and degraded. Binding was specific and saturable. After injection, labelled recombinant thrombopoietin was cleared much slower in c-Mpl-deficient than in normal mice. The data strongly support the concept that platelets regulate thrombopoietin levels via binding to C-Mpl receptors.
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Blood
, vol.87
, pp. 2154-2161
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Fielder, P.J.1
Gurney, A.L.2
Stefanich, E.3
Marian, M.4
Moore, M.W.5
Carver-Moore, K.6
De Sauvage, F.J.7
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Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand
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de Sauvage FJ, Mass PE, Spencer SD, Malloy BE, Gurney AL, Spencer SA, Darbonne WC, Henzel WJ, Wong SC, Kuang W, et al.: Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand. Nature 1994, 369:533-538.
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De Sauvage, F.J.1
Mass, P.E.2
Spencer, S.D.3
Malloy, B.E.4
Gurney, A.L.5
Spencer, S.A.6
Darbonne, W.C.7
Henzel, W.J.8
Wong, S.C.9
Kuang, W.10
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16
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0001694426
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The biological significance of truncated and full-length forms of Mpl ligands
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Edited by Kuter DJ, Hunt P, Sheridan W, Zucker-Franklin D. Totowa: Humana
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Foster D, Hunt P: The biological significance of truncated and full-length forms of Mpl ligands. In Thrombopoiesis and Thrombopoietins: Molecular, Cellular, Preclinical and Clinical Biology. Edited by Kuter DJ, Hunt P, Sheridan W, Zucker-Franklin D. Totowa: Humana; 1997:203-216.
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Thrombopoiesis and Thrombopoietins: Molecular, Cellular, Preclinical and Clinical Biology
, pp. 203-216
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Foster, D.1
Hunt, P.2
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17
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0029963122
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Combined administration of recombinant human megakaryocyte growth and development factor and granulocyte colony-stimulating factor enhances multilineage hematopoietic reconstitution in nonhuman primates after radiation-induced marrow aplasia
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Farese AM, Hunt P, Grab LB, MacVittle TJ: Combined administration of recombinant human megakaryocyte growth and development factor and granulocyte colony-stimulating factor enhances multilineage hematopoietic reconstitution in nonhuman primates after radiation-induced marrow aplasia. J Clin Invest 1996, 97:2145-2151. This was the first study to demonstrate that PEG-MGDF enhanced not only platelet recovery but neutrophil recovery after radiation of rhesus monkeys. Both bone marrow and peripheral blood progenitor cells of multiple lineages also were increased in PEG-MGDF-treated animals. These data also showed that PEG-MGDF was about 10-fold more active than the unmodified MGDF.
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J Clin Invest
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Farese, A.M.1
Hunt, P.2
Grab, L.B.3
MacVittle, T.J.4
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18
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0030024685
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Physiological regulation of early and late stages of megakaryocytopoiesis by thrombopoietin
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de Sauvage FJ, Carver-Moore K, Luoh S-M, Ryan A, Dowd M, Eaton DL, Moore MW: Physiological regulation of early and late stages of megakaryocytopoiesis by thrombopoietin. J Exp Med 1996, 183:651-656. This paper describes a "classic" experiment in which the thrombopoietin gene was "knocked-out" and complements this group's prior work in which c-Mpl-deficient mice were generated. Homozygous thrombopoietin-deficient mice had platelet counts 20% of normal, whereas heterozygous thrombopoietin-deficient mice had counts 60% of normal. This gene-dosage effect is the strongest evidence yet that the TPO gene is not regulated by the platelet count.
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J Exp Med
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, pp. 651-656
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De Sauvage, F.J.1
Carver-Moore, K.2
Luoh, S.-M.3
Ryan, A.4
Dowd, M.5
Eaton, D.L.6
Moore, M.W.7
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19
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0030048887
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Thrombopoietin in thrombocytopenic mice: Evidence against regulation at the mRNA level and for a direct regulatory role of platelets
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Stoffel R, Wiestner A, Skoda RC: Thrombopoietin in thrombocytopenic mice: evidence against regulation at the mRNA level and for a direct regulatory role of platelets. Blood 1996, 87:567-573.
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Blood
, vol.87
, pp. 567-573
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Stoffel, R.1
Wiestner, A.2
Skoda, R.C.3
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20
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Thrombocytopenia in c-Mpl-deficient mice
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Gurney AL, Carver-Moore K, de Sauvage FJ, Moore MW: Thrombocytopenia in c-Mpl-deficient mice. Science 1994, 265:1445-1447.
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Science
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Gurney, A.L.1
Carver-Moore, K.2
De Sauvage, F.J.3
Moore, M.W.4
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21
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0029897491
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Systemic hematologic effects of PEG-rHuMGDF-induced megakaryocyte hyperplasia in mice
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Ulich TR, del Castillo J, Senaldi G, Kintsler O, Yin S, Kaufman S, Tarpley J, Choi E, Kirley T, Hunt P, Sheridan WP: Systemic hematologic effects of PEG-rHuMGDF-induced megakaryocyte hyperplasia in mice. Blood 1996, 87:5006-5015.
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Blood
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Ulich, T.R.1
Del Castillo, J.2
Senaldi, G.3
Kintsler, O.4
Yin, S.5
Kaufman, S.6
Tarpley, J.7
Choi, E.8
Kirley, T.9
Hunt, P.10
Sheridan, W.P.11
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22
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10344235968
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Thrombopoietic effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) in patients with advanced cancer
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Basser RL, Rasko JEJ, Clarke K, Cebon J, Green MD, Hussein S, Alt C, Menchaca D, Tomita D, Marty J, Fox RM, Begley CG: Thrombopoietic effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) in patients with advanced cancer. Lancet 1996, 348:1279-1281. The first publication demonstrating the effect of Mpl ligands in humans. Seventeen cancer patients were injected with various doses of PEG-MGDF prior to chemotherapy. There was a dose-dependent rise in platelet count at effective doses of 0.3 and 1.0 μg/kg/d. There was no change in leukocyte or erythrocyte count. No patients experienced adverse effects.
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Lancet
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Basser, R.L.1
Rasko, J.E.J.2
Clarke, K.3
Cebon, J.4
Green, M.D.5
Hussein, S.6
Alt, C.7
Menchaca, D.8
Tomita, D.9
Marty, J.10
Fox, R.M.11
Begley, C.G.12
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23
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0028820319
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Regulation of platelet activation in vitro by the C-Mpl ligand, thrombopoietin
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Chen J, Herceg-Harjacek L, Groopman JE, Grabarek J: Regulation of platelet activation in vitro by the C-Mpl ligand, thrombopoietin. Blood 1995, 86:4054-4062.
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Chen, J.1
Herceg-Harjacek, L.2
Groopman, J.E.3
Grabarek, J.4
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0029049709
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Distinct regions of c-Mpl cytoplasmic domain are coupled to the JAK-STAT signal transduction pathway and She phosphorylation
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Gurney AL, Wong SC, Henzel WZ, DeSauvage FJ: Distinct regions of c-Mpl cytoplasmic domain are coupled to the JAK-STAT signal transduction pathway and She phosphorylation. Proc Nat Acad Sci U S A 1995, 92:5292-5296.
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Gurney, A.L.1
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25
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0028864865
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Megakaryocyte growth and development factor and interleukin-3 induce patterns of protein-tyrosine phosphorylation that correlate with dominant differentiation over proliferation of mpl-transfected 32D cells
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Mu SX, Xia M, Elliott G, Bogenberger J, Swift S, Bennett L, Lappinga DW, Hecht R, Lee R, Saris CJM: Megakaryocyte growth and development factor and interleukin-3 induce patterns of protein-tyrosine phosphorylation that correlate with dominant differentiation over proliferation of mpl-transfected 32D cells. Blood 1995, 86:4532-4543.
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Blood
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Mu, S.X.1
Xia, M.2
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Bogenberger, J.4
Swift, S.5
Bennett, L.6
Lappinga, D.W.7
Hecht, R.8
Lee, R.9
Saris, C.J.M.10
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26
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0029150706
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Thrombopoietin (TPO) induces tyrosine phosphorylation and activation of STATS and STAT3
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Bacon CM, Tortolani PJ, Shimosaka A, Rees RC, Longo DL, O'Shea JJ: Thrombopoietin (TPO) induces tyrosine phosphorylation and activation of STATS and STAT3. FEBS Letters 1995, 370:63-68.
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FEBS Letters
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Bacon, C.M.1
Tortolani, P.J.2
Shimosaka, A.3
Rees, R.C.4
Longo, D.L.5
O'Shea, J.J.6
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0029117375
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The thrombopoietin receptor c-MPL activates JAK2 and TYK2 tyrosine kinases
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Sattler M, Durstin MA, Frank DA, Okuda K, Kaushansky K, Salgia R, Griffin JD: The thrombopoietin receptor c-MPL activates JAK2 and TYK2 tyrosine kinases. Exp Hematol 1995, 23:1040-1048.
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Griffin, J.D.7
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A sensitive sandwich ELISA for measuring thrombopoietin in human serum: Serum thrombopoietin levels in healthy volunteers and in patients with haemopoietic disorders
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Tahara T, Usuki K, Sato H, Ohashi H, Morita H, Tsumura H, Matsumuto A, Miyazaki H, Urabe A, Kato T: A sensitive sandwich ELISA for measuring thrombopoietin in human serum: serum thrombopoietin levels in healthy volunteers and in patients with haemopoietic disorders. Br J Haematol 1996, 93:783-788. The first sensitive ELISA for thrombopoietin is described here and the TPO levels in normal patients and those with a wide range of hematological disorders are described.
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Br J Haematol
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Tahara, T.1
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Randomized, double-blind, placebo-controlled phase I trial of pegylated megakaryocyte growth and development factor administered to patients with advanced cancer after chemotherapy
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Begley G, Basser R, Clarke K, Rasko J, Green M, Grigg A, Cebon J, Marty J, Menchaca D, Tomita D, Fox R: Randomized, double-blind, placebo-controlled phase I trial of pegylated megakaryocyte growth and development factor administered to patients with advanced cancer after chemotherapy [abstract]. Proc Am Soc Clin Oncol 1996, 15:271.
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Effects of polyethylene glycolconjugated recombinant human megakaryocyte growth and development factor on platelet counts after chemotherapy for lung cancer
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Fanucci M, Glaspy J, Crawford J, Garst J, Figlin R, Sheridan W, Menchaca D, Tomita D, Ozer H, Harker L: Effects of polyethylene glycolconjugated recombinant human megakaryocyte growth and development factor on platelet counts after chemotherapy for lung cancer. New Engl J Med 1997, 336:404-409.
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Single-dose therapy with recombinant human thrombopoietin (rhTPO) in patients receiving cytotoxic chemotherapy
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Vadhan-Raj S, Burris H, Benjamin RS, Patel RS, Johnson T, Hellmann S, Cohen R, Watanabne B, Von Hoff D: Single-dose therapy with recombinant human thrombopoietin (rhTPO) in patients receiving cytotoxic chemotherapy [abstract]. Proc Am Soc Clin Oncol 1996, 15(suppl 1):24.
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Chronic exposure to retroviral vector encoded MGDF (mpl-ligand) induces lineage-specific growth and differentiation of megakaryocytes in mice
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Van X-Q, Lacey D, Fletcher F, Hartley C, McElroy P, Sun Y, Xia M, Mu S, Saris C, Hill D, Hawley RG, McNiece IK: Chronic exposure to retroviral vector encoded MGDF (mpl-ligand) induces lineage-specific growth and differentiation of megakaryocytes in mice. Blood 1995, 86:4025-4033.
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Thrombopoietin receptor expression in human cancer cell lines and primary tissues
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Vigon I, Dreyfus F, Melle J, Viguie F, Ribrag V, Cocault L, Souryi M, Gisselbrecht S: Expression of the C-Mpl proto-oncogene in human hematologic malignancies. Blood 1993, 82:877-883.
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Prognostic value of c-Mpl expression in myelodysplastic syndromes
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Bouscary D, Preudhomme C, Ribrag V, Melle J, Viguie F, Picard F, Guesnu M, Fenaux P, Gisselbrecht S, Dreyfus F: Prognostic value of c-Mpl expression in myelodysplastic syndromes. Leukemia 1995, 9:783-788.
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Growth response of acute myeloblastic leukemia cells to recombinant human thrombopoietin
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39
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0029560144
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Expression of c-Mpl and c-Mpl ligand gene in hematopoietic cells of individuals with and without myeloproliferative disorders and leukemia cell lines
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40
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0028803099
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Hokom MM, Lacey D, Kinstler OB, Choi E, Kaufman S, Faust J, Rowan C, Dwyer E, Nichol JL, Grasel T, et al.: Pegylated megakaryocyte growth and development factor abrogates the lethal thrombocytopenia associated with carboplatin and irradiation in mice. Blood 1995, 86:4486-4492. The log-linear dose response relationship of PEG-MGDF and MGDF is described in normal mice. Using a moderately severe model of chemotherapy-and radiation-induced thrombocytopenia, PEG-MGDF reduced the depth of the platelet nadir and the duration of thrombocytopenia. In addition, neutropenia and anemia were reduced.
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41
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Accelerated reconstitution of platelets and erythrocytes after syngeneic transplantation of bone marrow cells derived from thrombopoietin pretreated donor mice
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Fibbe WE, Heemskerk DPM, Laterveer L, Pruijt JFM, Foster D, Kaushansky K, Willemze R: Accelerated reconstitution of platelets and erythrocytes after syngeneic transplantation of bone marrow cells derived from thrombopoietin pretreated donor mice. Blood 1995, 86:3308-3313. An excellent study of the effect of rTPO in mice undergoing bone marrow transplantation. Use of rTPO after transplantation did not alter platelet engraftment. Pretreatment of donor mice with rTPO did enhance engraftment of recipients and suggests a potential application of Mpl ligands in transplantation.
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45
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46
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48
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Choi ES, Hokom M, Bartley T, Li Y-S, Ohashi H, Kato T, Nichol JL, Skrine J, Knudten A, Chen J, Hornkohl A, Grampp G, Sleeman L, Cole S, Trail G, Hunt P: Recombinant human megakaryocyte growth and development factor (rHuMQDF), a ligand for c-Mpl, produces functional human platelets in vitro. Stem Cells 1995, 13:317-322.
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