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Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand
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Kaushansky K, Lok SI, Holly RD, Broudy VC, Lin N, Bailey MC, Forstrom JW, Buddle MM, Oort PJ, Hagen FS, et al.: Promotion of megakaryocyte progenitor expansion and differentiation by the C-Mpl ligand thrombopoietin. Nature 1994, 369:568-571.
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Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor Mpl
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Bartley TD, Bogenberger J, Hunt P, Li YS, Lu HS, Martin F, Chang MS, Samal B, Nichol JL, Swift S, et al.: Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor Mpl. Cell 1994, 77:1117-1124.
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The purification of megapoietin: A physiological regulator of megakaryocyte growth and platelet production
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Ulich TR, Castillo J, Yin S, Swift S, Padilla D, Senaldi G, Bennett L, Shuter •• J, Bogenberger J, Sun D, et al.: Megakaryocyte growth and development factor ameliorates carboplatin-induced thrombocytopenia in mice. Blood 1995, 86:971-976. Demonstrates 1) that a single dose of recombinant c-mpl ligand can substantially elevate the platelet count in normal animals; 2) a plateau in the dose-response curve in normal animals; and 3) efficacy of recombinant c-mpl ligand in accelerating platelet recovery following myelosuppressive chemotherapy.
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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. In a particularly stringent murine model of iatrogenic thrombocytopenia, recombinant c-mpl ligand accelerated platelet recovery and significantly improved survival. This model also demonstrates that r-metHuG-CSF can effectively be used in combination with recombinant c-mpl ligand to reduce the severity of both neutropenia and thrombocytopenia.
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Ulich TR, Del Castillo J, Senaldi G, Kinstler OB, Yin S, Kaufman S, Tarpley J, Choi E, Hunt P, Sheridan WP: Systemic hematologic effects of MGDF-induced megakaryocyte hyperplasia in mice. Blood 1996, in press.
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Ulich, T.R.1
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Gurney AL, Carver-Moore K, De Sauvage FJ, Moore MW: •• Thrombocytopenia In c-mpl-deflcient mice. Science 1994, 265:1445-1447. This critical study proves that the c-mpl receptor is essential for normal platelet production but not for other blood cell lineages. The low but detectable platelet counts in this knockout mouse suggest redundancy in the regulation of platelet production.
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De Sauvage FJ, Luoh SM, Carver-Moore K, Ryan A, Dowd M, Eaton DL, • Moore MW: Deficiencies in early and late stages of megakaryocytopolesis in TPO-KO mice [abstract]. Blood 1995, 86:255a. A complement to the study by Gurney et al. (Science 1994, 265:1445-1447) that confirms that c-mpl ligand is critical for platelet production but that a low level of platelet production is maintained in its absence.
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De Sauvage, F.J.1
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Yan XQ, Lacey D, Fletcher F, Hartley CA, 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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Farese AM, Hunt P, Bone T, MacVittie TJ: Recombinant human •• megakaryocyte growth and development factor stimulates thrombocytopoiesis in normal nonhuman primates. Blood 1995, 86:54-59. The first study to demonstrate the in vivo activity of recombinant c-mpl ligand in normal primates, including an increase in certain bone marrow progenitors.
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Farese, A.M.1
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Prediction of a threshold and optimally effective thrombocytopoietic dose of recombinant human thrombopoietin (rhTPO) in nonhuman primates based on murine pharmacokinetic data
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Winton EF, Thomas GR, Marian ML, Bucur SZ, McClure HM, Eaton DL: Prediction of a threshold and optimally effective thrombocytopoietic dose of recombinant human thrombopoietin (rhTPO) in nonhuman primates based on murine pharmacokinetic data [abstract]. Exp Hematol 1995, 23:879.
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Winton, E.F.1
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Harker LA, Marzec UM, Hunt P, Kelly AB, Tomer A, Hanson SR, Stead RB: •• Regulation of platelet production and function by megakaryocyte growth and development factor (MGDF) in nonhuman primates. Blood 1996, 87:1833-1844. The first detailed study of the in vivo effects of recombinant c-mpl ligand on megakaryocytopoiesis and platelet function in a nonhuman primate.
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Blood
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Harker, L.A.1
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Hanson, S.R.6
Stead, R.B.7
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Dose-response effects of pegylated human megakaryocyte growth and development factor (PEG-rHuMGDF) 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 human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production and function in nonhuman primates. Blood 1996, in press. A comprehensive study of the dose-response effects of recombinant c-mpl ligand on the kinetics of megakaryocytopoiesis, platelet function, and the potential for thrombogenicity. Although there is in vitro evidence of enhanced sensitivity to platelet pro-aggregatory stimuli, the platelet deposition on thrombogenic surfaces is proportional to the platelet count without in vivo evidence of enhanced platelet function.
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Blood
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Harker, L.A.1
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Hunt, P.3
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Cheung, E.6
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Stead, R.B.8
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Effects of recombinant human thrombopoietin (rhTPO) and granulocyte colony-stimulating factor (rHuG-CSF) on pancytopenia induced by chemotherapy
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Akahori H, Kabaya K, Shibuya K, Obuchi M, Kato T: Effects of recombi• nant human thrombopoietin (rhTPO) and granulocyte colony-stimulating factor (rHuG-CSF) on pancytopenia induced by chemotherapy [abstract]. Blood 1995, 86:892a. Confirms that recombinant c-mpl ligand can be used effectively with r-metHuG-CSF in another stringent murine chemotherapy model.
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Blood
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Akahori, H.1
Kabaya, K.2
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Evaluation of thrombopoietin (TPO) in murine models of thrombocytopenia induced by whole body irradiation and cancer chemotherapeutic agents
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Thibodeaux H, Mathias J, Eaton DL, Thomas GR: Evaluation of thrombopoietin (TPO) in murine models of thrombocytopenia induced by whole body irradiation and cancer chemotherapeutic agents [abstract]. Blood 1995, 86:497a.
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Thibodeaux, H.1
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0348192686
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Effects of the combined administration of TPO and G-CSF on recovery from myelosuppression in mice
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Grossmann A, Lenox JS, Humes J, Ren HP, Kaushansky K, Sprugel KH: Effects of the combined administration of TPO and G-CSF on recovery from myelosuppression in mice [abstract]. Blood 1995, 86:371a.
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Blood
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Grossmann, A.1
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Effects of treatment with MGDF and G-CSF on the acceleration of simultaneous neutrophil and platelet recovery after bone marrow transplant in mice
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Molineux G, Hartley CA, McElroy P, McCrea C, McNiece IK: Effects of • treatment with MGDF and G-CSF on the acceleration of simultaneous neutrophil and platelet recovery after bone marrow transplant in mice [abstract]. Blood 1996, 86:227a. In a murine bone marrow transplant model, the combination of recombinant c-mpl ligand and r-metHuG-CSF resulted in accelerated platelet and leukocyte recovery compared with either agent alone.
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Blood
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Molineux, G.1
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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.
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Fibbe, W.E.1
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Foster, D.5
Kaushansky, K.6
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24
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0348192674
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Improvement of thrombocytopenia after bone marrow-transplantation by recombinant human thrombopoietin (rhTPO) in mice
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Kabaya K, Akahori H, Shibuya K, Nitta Y, Kusaka M, Kato T, Miyazaki H: Improvement of thrombocytopenia after bone marrow-transplantation by recombinant human thrombopoietin (rhTPO) in mice [abstract]. Blood 1995, 86:114a.
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Kabaya, K.1
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1842411028
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Molineux G, Hartley CA, McElroy P, McCrea C, McNiece IK: Megakaryocyte growth and development factor (MGDF) accelerates platelet recovery in peripheral blood progenitor cell (PBPC) transplant recipients [abstract]. Blood 1995, 86:461a. In a murine model of peripheral blood progenitor cell transplantation, recombinant c-mpl ligand had a modest effect on mobilization but was particularly effective in accelerating platelet recovery when administered after peripheral blood progenitor cell transplantation.
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Blood
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Molineux, G.1
Hartley, C.A.2
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8944251950
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Enhancement of hematopoietic reconstitution in nonhuman primates following radiation-induced marrow aplasia by the combined administration of recombinant human megakaryocyte growth and development factor and granulocyte colony stimulating factor
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Farese AM, Hunt P, Grab LB, MacVittie TJ: Enhancement of hematopoi•• etic reconstitution in nonhuman primates following radiation-induced marrow aplasia by the combined administration of recombinant human megakaryocyte growth and development factor and granulocyte colony stimulating factor. J Clin Invest 1996, in press. The combination of recombinant c-mpl ligand and r-metHuG-CSF resulted in accelerated platelet and neutrophil recovery following sublethal irradiation in rhesus monkeys. Neutrophils recovered more rapidly with the combination than with r-metHuG-CSF alone.
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Farese, A.M.1
Hunt, P.2
Grab, L.B.3
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0347563155
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Evaluation of administration protocols of pegylated-megakaryocyte growth and development factor on platelet recovery in a primate model of radiation-induced bone marrow aplasia
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Farese AM, Hunt P, Grab LB, MacVittie TJ: Evaluation of administration • protocols of pegylated-megakaryocyte growth and development factor on platelet recovery in a primate model of radiation-induced bone marrow aplasia [abstract]. Blood 1995, 86:497a. Administration of recombinant c-mpl ligand three times a week for 2 weeks was at least as effective as daily administration in this well-characterized model. In fact, erythrocyte recovery may be enhanced by this alternative regimen.
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Blood
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Farese, A.M.1
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Enhanced hematopoietic regeneration in primate model of myelosuppressive chemotherapy by pegylated recomblnant human megakaryocyte growth and development factor (PEG-rHuMGDF) in combination with granulocyte colony stimulating factor (G-CSF)
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Harker LA, Marzec UM, Kelly AB, Hanson SR: Enhanced hematopoietic • regeneration in primate model of myelosuppressive chemotherapy by pegylated recomblnant human megakaryocyte growth and development factor (PEG-rHuMGDF) in combination with granulocyte colony stimulating factor (G-CSF) [abstract]. Blood 1995, 86:497a. An important study that demonstrates that there may be interactions between r-metHuG-CSF and recombinant c-mpl, particularly when stem cell reserves are limited. Full efficacy of both agents could be maintained by altering the cytokine regimen. With the opitmal regimens, platelet counts actually increased substantially following hepsulfam chemotherapy. This study indicates that cytokine combinations may need to be optimized with different myelosuppressive and myeloablative regimens.
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Blood
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Harker, L.A.1
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Andrews RG, Winkler A, Woogerd P, Briddell RA, Myerson DA, Knitter GH, McNiece IK, Hunt P: Recombinant human megakaryocyte growth and development factor (rHuMGDF) stimulates thrombopoiesis in normal baboons and accelerates platelet recovery after chemotherapy [abstract]. Blood 1995, 86:371a.
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Andrews, R.G.1
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Neelis KJ, Wognum AW, Eaton DL, Thomas R, Wagemaker G: Preclinical evaluation of thrombopoietin in rhesus monkeys [abstract]. Blood 1995, 86:256a.
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Pallard C, Gouilleux F, Benit L, Cocault L, Souyn M, Levy D, Groner B, Gisselbrecht S, Dusanter-Fourt I: Thrombopoietin activates a STAT5-like factor in hematopoietic cells. EMBO J 1995, 14:2847-2856.
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Drachman JG, Griffin JD, Kaushansky K: The c-Mpl ligand (thrombopoietin) stimulates tyrosine phosphorylation of Jak2, Shc, and c-Mpl. J Biol Chem 1995, 270:4979-4982.
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Toombs C, Young CH, Glaspy JA, Varnum BC: Megakaryocyte growth and development factor (MGDF) moderately enhances in vitro platelet aggregation. Thromb Res 1995, 80:23-33.
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Toombs C, Lott FD, Nelson AG, Stead RB: Megakaryocyte growth and •• development factor (MGDF) promotes platelet production in vivo without affecting in vivo thrombosis [abstract]. Blood 1995, 86:369a. One of the few studies that has evaluated the potential thrombogenic effects of recombinant c-mpl ligand in vivo. Despite evidence of enhanced ex vivo sensitivity of platelets to proaggretory stimuli in these animals, there was no in vivo evidence of enhanced platelet adhesion or thrombogenicity.
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Blood
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