In vivo effects of Mpl ligand administration and emerging clinical applications for the Mpl ligands.
The Mpl ligands are a family of closely related hematopoietic growth factors that bind to the thrombopoietin receptor, c-Mpl. In addition to the endogenous Mpl ligand, thrombopoietin, two recombinant Mpl ligands, recombinant thrombopoietin and pegylated megakaryocyte growth and development factor (PEG-MGDF) are under investigation. Endogenous thrombopoietin regulates most of the normal production of platelets but also is essential for the normal development of other lineages. When recombinant thrombopoietin or PEG-MGDF is administered to normal animals or humans, there is a dose-dependent increase in the platelet count but no effect on leukocytes or erythrocytes. When administered following chemotherapy in animal models or humans, Mpl ligands reduce the duration and sometimes the degree of thrombocytopenia. The Mpl ligands also may be effective in reducing the thrombocytopenia of patients with HIV infection, liver disease, myelodysplasia, or after plateletpheresis.
Kuter
D J
DJ
Hematology/Oncology Division, Massaohusetts General Hospital Cancer Center, Boston 02114, USA.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D009363:Neoplasm Proteins; D011092:Polyethylene Glycols; D011518:Proto-Oncogene Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012016:Reference Values; D013926:Thrombopoietin / Q000009:adverse effects / Q000502:physiology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; C082218:MPL protein, human; D011092:Polyethylene Glycols; D013926:Thrombopoietin