Megakaryocyte growth and development factor (MGDF): an Mpl ligand and cytokine that regulates thrombopoiesis

Megakaryocyte growth and development factor (MGDF) is a ligand for the Mpl receptor related to thrombopoietin (TPO). MGDF stimulates megakaryocytopoiesis and thrombopoiesis, and is highly selective to cells bearing the Mpl receptor. Studies done in rodents, nonhuman primates, and humans have confirmed that MGDF can increase platelet counts in normal and chemotherapy- or radiotherapy-treated subjects. Platelet function and physiology remain normal after MGDF administration, with no effect on platelet aggregation. Pegylated recombinant human MGDF (PEG-rHuMGDF) was used clinically with initial success. Cancer patients receiving chemotherapy showed dose-dependent increases in platelet counts and increases in bone marrow megakaryocytes. Clinical development of PEG-rHuMGDF was halted owing to the formation of neutralizing antibodies in some patients and normal volunteers who received the drug. The application of exogenous recombinant Mpl ligands should be explored in the setting of randomized clinical trials and the findings extended to mobilization of CD34+ stem cells, ex vivo expansion techniques, and use in platelet abnormalities.