Biologic and structural differences of thrombopoietic growth factors.
The search for a thrombopoietic agent has resulted in the identification of numerous cytokines and growth factors with thrombopoietic activity. However, with the exception of interleukin (IL)-11 and thrombopoietin (TPO), the megakaryopoietic activity of most of these molecules has not produced clearly identifiable clinical benefits. Despite the relatively modest effect of IL-11 on megakaryocyte and platelet production in vitro and in vivo, it does reduce the need for platelet transfusions in specialized clinical settings. In contrast, the c-Mpl ligand TPO has been shown to be a potent stimulator of megakaryocyte and platelet production both in vitro and in vivo. Clinical studies are being conducted with two different preparations of the c-Mpl ligand: recombinant human thrombopoietin (rhTPO) and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF). A recombinant form of the complete human molecule, rhTPO is glycosylated and produced in mammalian cells. PEG-rHuMGDF consists of only the receptor-binding domain linked to a polyethylene glycol (PEG) moiety and is generated in Escherichia coil. Although c-Mpl ligands are still being evaluated, preliminary evidence indicates that these molecules can elevate platelet counts and may be useful in a range of clinical contexts. This report discusses aspects of the biology behind the clinical actions of IL-11 and the c-Mpl ligands.
Begley
C G
CG
Centre for Developmental Cancer Therapeutics, Parkville, Victoria, Australia.
Basser
R L
RL
D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects*; D016207:Cytokines / Q000097:blood / Q000494:pharmacology / Q000502:physiology; D006133:Growth Substances / Q000097:blood / Q000494:pharmacology* / Q000502:physiology; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D017370:Interleukin-11 / Q000097:blood / Q000494:pharmacology / Q000502:physiology; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects*; D013926:Thrombopoietin / Q000097:blood / Q000494:pharmacology / Q000502:physiology
D016207:Cytokines; D006133:Growth Substances; D017370:Interleukin-11; D013926:Thrombopoietin