THE STRUCTURE, BIOLOGY AND POTENTIAL THERAPEUTIC APPLICATIONS OF RECOMBINANT THROMBOPOIETIN

Platelets, an integral component of hemostasis, are produced by megaka ryocytes derived from the differentiation of pluripotent stem cells in the bone marrow or spleen. After decades of study, the regulation of this process is still not well understood. However, the recent cloning and characterization of thrombopoietin, a ligand for the receptor enc oded by the c-mpl proto-oncogene, provides new insights into the humor al regulation of megakaryocytopoiesis and platelet production. Consist ent with the proposed role as a major physiological regulator of megak aryocytopoiesis, thrombopoietin has potent effects on megakaryocytopoi esis in vitro and in vivo. In addition to the original supposition tha t thrombopoietin functions as a late-acting megakaryocyte maturation f actor, recombinant thrombopoietin proves also to be a potent stimulato r of hematopoietic progenitor cells, inducing them to undergo prolifer ation and differentiation into megakaryocytic colonies. When administe red to mice, thrombopoietin causes an increase in peripheral platelet numbers to previously unattainable levels within a few days. Studies o f the efficacy of thrombopoietin are underway. It is envisaged that th is new cytokine will have widespread applications as a therapeutic age nt for the management of bleeding due to thrombocytopenias, in particu lar those resulting from cancer chemo- or irradiation therapy.