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Thrombopoietin: Biology and Clinical Applications

Hematology/Oncology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA

Correspondence: David J. Kuter, M.D., D.Phil., Hematology/Oncology Unit, Cox 621, Massachusetts General Hospital, Fruit Street, Boston, MA 02114, USA. Telephone: 617-726-8743; Fax: 617-724-3166.

Thrombopoietin (also called c-Mpl ligand, megakaryocyte growth and development factor, megapoietin) has recently been purified and cloned. This molecule is indeed the long-sought-after hematopoietic factor that controls platelet production. Thrombopoietin levels increase within 24 h after the onset of thrombocytopenia and are inversely and exponentially proportional to the platelet count. Injection of thrombopoietin into animals stimulates the number, size and ploidy of bone marrow megakaryocytes and increases the platelet count up to ten-fold. Although human studies with several different forms of recombinant thrombopoietin have just begun, animal studies suggest a wide range of potential clinical applications. In animals, recombinant thrombopoietin reduced radiation- and chemotherapy-induced thrombocytopenia, enhanced platelet recovery after bone marrow transplantation and increased the number of megakaryocyte precursor cells in stem cell harvests. Active at very low concentrations, thrombopoietin appears to have few adverse effects in animals. At very high doses, reversible marrow fibrosis has occasionally been seen, but despite platelet counts up to ten times normal, there is no evidence that it increased the risk of thrombosis. There is little likelihood that thrombopoietin will stimulate tumor growth since receptors for thrombopoietin have not been detected on solid tumors. Therefore, thrombopoietin promises to be a specific and effective stimulator of platelet production and will soon join erythropoietin and G/GM-CSF in the clinical armamentarium. Although thrombocytopenia is uncommon in most chemotherapy protocols, ongoing clinical studies will determine the role of thrombopoietin in the prevention and treatment of thrombocytopenia in oncology patients.

Key Words. Thrombopoietin • Platelets • Megakaryocytes • Hematopoiesis • Cytokines • Chemotherapy • Growth factors