THROMBOPOIETIN - BIOLOGY AND POTENTIAL CLINICAL-APPLICATIONS

After art almost 40-year search for a primary regulatory of platelet p roduction, thrombopoietin has recently been purified and cloned. Throm bopoietin regulates all stages in the production of platelets by promo ting both the proliferation of megakaryocyte progenitors and their mat uration into platelet-producing megakaryocytes, Irt preclinical studie s in normal mice and nonhuman primates, administration of thrombopoiet in resulted in a rapid rise in platelet counts to levels previously un attainable with other thrombopoietic cytokines, In myelosuppressed ani mal models, use of thrombopoietin following chemotherapy, radiation, o r stem-cell transplantation accelerated megakaryocyte and platelet rec overy. Thrombopoietin has rapidly moved from the laboratory to the cli nic in the last 3 years. Preliminary results of clinical trials using truncated or full-length forms of the molecule indicate that thrombopo ietin is a powerful stimulus to the production of megakaryocytes and n ormal platelets in humans and enhances platelet recovery following che motherapy, Although the peripheral effect is selective on platelet lin eage, thrombopoietin mediates stimulatory effects on progenitors of mu ltiple cell lineages at the bone marrow level and mobilizes progenitor cells into the peripheral blood, These biological effects suggest tha t thrombopoietin holds promise as a useful agent for the prevention an d treatment of thrombocytopenia in cancer patients and for other disor ders of thrombocytopenia.