[Thrombopoietin--a further advance in support therapy]

The existence of humoral mediator of thrombopoiesis was suggested almost 40 years ago, but the attempts at its identification remained unsuccessful. In 1986 a retroviral complex that induced a myeloproliferative syndrome in recipient mice was described. Subsequently the viral oncogene responsible for the disorder was identified and its human cellular homologue c-mpl was cloned. Based on the laboratory findings the critical role of c-mpl a c-mpl ligand (ML) in megakaryopoiesis was suggested. In 1994 five groups cloned or purified ML and the results of following studies clearly indicate that it possesses the characteristics of long-sought thrombopoietin (TPO). In vitro ML induce both proliferation and maturation of megakaryocytes progenitors. It acts synergistically or additively with some other growth factors, especially with early acting cytokines like IL-3 or stem cell factor. Like in other hematopoietic regulators the stimulatory effect of TPO on other hematopoietic lineages was observed. However, some laboratory data point to the possible role of TPO in leukemogenesis. The effect of TPO was confirmed by multiple laboratory in vivo studies. At the end of 1996 the first promising results of clinical trials were published. The preclinical and early human clinical studies indicate that the newly available stimulator of platelet production will probably be beneficial in many disease and syndromes. The evaluation of the safety and the efficacy of TPO in clinical practice might be available in a short time.