Thrombopoietin : Signal Transduction and Clinical Applications

Abstract

TPO induces tyrosine phosphorylation of numerous signaling molecules and activates the Ras/MAPK and JAK/STAT signal pathways through its Mpl receptor. TPO specific signaling is as yet unknown. Serum TPO levels may be regulated by bone marrow megakaryocytes and platelets through binding to the Mpl receptor expressed on their surface membrane. But the expression of murine and human TPO mRNA is increased in bone marrow and not the liver under thrombocytopenic conditions, indicating that there is another mechanism for the regulation of TPO. Pegylated TPO (PEG-rHuMGDF) and full-length glycosylated recombinant TPO were used in clinical applications. The patients with cancer who received TPO showed an increase in platelet count or shortening of the duration of platelet recovery in a dose-dependent manner and without apparent side effects. The functions of the platelets were normal. These results indicate that TPO might be useful in clinical applications.