Thrombopoietin: biology and potential clinical applications.
After an almost 40-year search for a primary regulatory of platelet production, thrombopoietin has recently been purified and cloned. Thrombopoietin regulates all stages in the production of platelets by promoting both the proliferation of megakaryocyte progenitors and their maturation into platelet-producing megakaryocytes. In preclinical studies in normal mice and non-human primates, administration of thrombopoietin resulted in a rapid rise in platelet counts to levels previously unattainable with other thrombopoietic cytokines. In myelosuppressed animal models, use of thrombopoietin following chemotherapy, radiation, or stem-cell transplantation accelerated megakaryocyte and platelet recovery. Thrombopoietin has rapidly moved from the laboratory to the clinic in the last 3 years. Preliminary results of clinical trials using truncated or full-length forms of the molecule indicate that thrombopoietin is a powerful stimulus in the production of megakaryocytes and normal platelets in humans and enhances platelet recovery following chemotherapy. Although the peripheral effect is selective on platelet lineage, thrombopoietin mediates stimulatory effects on progenitors of multiple cell lineages at the bone marrow level and mobilizes progenitor cells into the peripheral blood. These biological effects suggest that thrombopoietin holds promise as a useful agent for the prevention and treatment of thrombocytopenia in cancer patients and for other disorders of thrombocytopenia.
Prow
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Department of genitourinary Medical Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, USA.
Vadhan-Raj
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D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D002986:Clinical Trials as Topic; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000209:etiology / Q000517:prevention & control*; D013926:Thrombopoietin / Q000494:pharmacology* / Q000627:therapeutic use
D011994:Recombinant Proteins; D013926:Thrombopoietin