Biologic effects of thrombopoietin, the Mpl ligand, and its therapeutic potential

In vitro experiments and data from studies in Mpl-null and thrombopoietin (TPO)-null mice have shown that TPO is the major regulator of megakaryocytopoiesis. In addition to its effect on megakaryocyte production and maturation, TPO has a proliferative effect on other progenitors, particularly erythroid progenitors, when used in combination with other cytokines (erythropoietin, interleukin 3, and kit ligand). The precise effect of TPO on platelet release is uncertain and warrants further study. In myeloablated animal models (mice and primates), TPO shortened the period of critical neutrocytopenia and accelerated the recovery of platelet counts, thereby showing great promise for use in patients postchemotherapy and posttransplantation.