Thrombopoietin: biological and preclinical properties.
The characterization and purification of thrombopoietin (TPO) was problematic due to the extremely low levels of protein present in even the richest physiologic sources of the material and to the complex nature of plasma as a starting material for biochemical purification. Although interleukin-3 (IL-3) can initiate megakaryocytic progenitor cell development, it cannot complete this process. TPO is absolutely essential for full theory to clinical trials, and many of the properties predicted by early investigators using semipurified preparations of plasma-derived material have been verified using recombinant protein. TPO increases the size, ploidy, and cell-surface expression of platelet-specific proteins. TPO also stimulates the proliferation of megakaryocytic progenitor cells and augments the erythroid progenitor response to erythropoietin and other early-acting cytokines. TPO levels are inversely related to platelet mass; the recombinant protein stimulates thrombopoiesis and, to a lesser extent, erythropoiesis. Preliminary findings give reason for optimism, but clinical trials will be required to establish the usefulness of this primary regulator of platelet production in hastening hematopoietic recovery in states of natural and iatrogenic marrow failure.
Kaushansky
K
K
Division of Hematology, University of Washington School of Medicine, Seattle 98195, USA.
D000818:Animals; D001792:Blood Platelets / Q000502:physiology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology / Q000502:physiology; D008533:Megakaryocytes / Q000166:cytology*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013926:Thrombopoietin / Q000494:pharmacology* / Q000502:physiology* / Q000627:therapeutic use
D007377:Interleukin-3; D011994:Recombinant Proteins; D013926:Thrombopoietin