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Blood, 1 June 2007, Vol. 109, No. 11, pp. 4607-4616. Prepublished online as a Blood First Edition Paper on February 8, 2007; DOI 10.1182/blood-2006-10-019315. This Article Full Text (PDF) All Versions of this Article: blood-2006-10-019315v1 109/11/4607    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kuter, D. J. Search for Related Content PubMed PubMed Citation Articles by Kuter, D. J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 24, 2006 Accepted January 31, 2007 New thrombopoietic growth factors David J. Kuter* Hematology Division, Massachusetts General Hospital, Boston, MA, United States * Corresponding author; email: kuter.david{at}mgh.harvard.edu. Although development of first generation thrombopoietic growth factors [recombinant human thrombopoietin (TPO) and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF)] was stopped due to development of antibodies to PEG-rHuMGDF, non-immunogenic second generation thrombopoietic growth factors with unique pharmacological properties have been developed. TPO peptide mimetics contain TPO receptor-activating peptides inserted into complementarity-determining regions of Fab (Fab 59), attached to the IgG Fc region (AMG 531), or pegylated (Peg-TPOmp). Orally available, TPO non-peptide mimetics (eltrombopag, AKR-501) bind and activate the TPO receptor by a mechanism different from TPO and may have an additive effect to TPO. TPO agonist antibodies are monoclonal antibodies activating the TPO receptor but modified in size [TPO minibodies, ie VB22B sc(Fv)2] or immunoglobuln type (domain subclass-converted TPO agonist antibodies, ie MA01G4G344). All second generation thrombopoietic growth factors stimulate growth of TPO-dependent cell lines via JAK2/STAT signaling pathways and increase platelet counts in animals. When tested in healthy humans, TPO peptide and non-peptide mimetics produced a dose-dependent rise in platelet count. AMG 531 and eltrombopag markedly increase platelet counts in patients with immune thrombocytopenic purpura, without significant adverse effects. One or more second generation thrombopoietic growth factors should soon be clinically available for treating thrombocytopenic disorders. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. J. Kuter, G. J. Mufti, B. J. Bain, R. P. Hasserjian, W. Davis, and M. Rutstein Evaluation of bone marrow reticulin formation in chronic immune thrombocytopenia patients treated with romiplostim Blood, October 29, 2009; 114(18): 3748 - 3756. [Abstract] [Full Text] [PDF] S. Perreault and J. Burzynski Romiplostim: A novel thrombopoiesis-stimulating agent Am. J. Health Syst. Pharm., May 1, 2009; 66(9): 817 - 824. [Abstract] [Full Text] [PDF] C. Marty, R. Chaligne, C. Lacout, S. N. Constantinescu, W. Vainchenker, and J.-L. Villeval Ligand-independent Thrombopoietin Mutant Receptor Requires Cell Surface Localization for Endogenous Activity J. Biol. Chem., May 1, 2009; 284(18): 11781 - 11791. [Abstract] [Full Text] [PDF] H. J Ipema, M. Y Jung, and A. E Lodolce Romiplostim Management of Immune Thrombocytopenic Purpura Ann. Pharmacother., May 1, 2009; 43(5): 914 - 919. [Abstract] [Full Text] [PDF] J. Burzynski New options after first-line therapy for chronic immune thrombocytopenic purpura Am. J. Health Syst. Pharm., January 15, 2009; 66(2_Supplement_2): S11 - S21. [Abstract] [Full Text] [PDF] J. N. George and D. R. Terrell Novel thrombopoietic agents: a new era for management of patients with thrombocytopenia Haematologica, October 1, 2008; 93(10): 1445 - 1449. [Full Text] [PDF] A. Yamane, T. Nakamura, H. Suzuki, M. Ito, Y. Ohnishi, Y. Ikeda, and Y. Miyakawa Interferon-{alpha}2b-induced thrombocytopenia is caused by inhibition of platelet production but not proliferation and endomitosis in human megakaryocytes Blood, August 1, 2008; 112(3): 542 - 550. [Abstract] [Full Text] [PDF] M. Drouet, C. Delaunay, N. Grenier, P. Garrigou, J.-F. Mayol, and F. Herodin Cytokines in combination to treat radiation-induced myelosuppresssion: evaluation of SCF + glycosylated EPO + pegylated G-CSF as an emergency treatment in highly irradiated monkeys Haematologica, March 1, 2008; 93(3): 465 - 466. [Abstract] [Full Text] [PDF] M. A. Blajchman, S. J. Slichter, N. M. Heddle, and M. F. Murphy New Strategies for the Optimal Use of Platelet Transfusions Hematology, January 1, 2008; 2008(1): 198 - 204. [Abstract] [Full Text] [PDF]

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