title: Thrombopoietin: accumulating evidence for an important biological effect on the hematopoietic stem cell.
abstract: Although it is clear that thrombopoietin is the primary regulator of thrombopoiesis, several lines of evidence indicate that the hormone affects multiple aspects of hematopoiesis: the in vivo administration of TPO increases marrow levels of erythroid, myeloid, and megakaryocytic progenitor cells and its genetic elimination or that of its receptor (c-mpl) reduces the numbers of these cells; all hematopoietic stem cells (HSCs) are c-mpl+; genetic elimination of c-mpl reduces the numbers of murine HSCs by 7-8-fold; and its null mutation in humans leads to congenital amegakaryocytic thrombocytopenia, a disorder that almost invariably leads to aplastic anemia. Recently, we have begun to explore the role of TPO in the HSC self-renewal and expansion that characterizes the post-stem-cell-transplantation period. Using limiting dilution cell transplantation analyses, we found that HSC self-renewal and expansion is reduced 10-20-fold after transplantation of normal stem cells into tpo null mice compared to their wild-type counterparts. Although the molecular mechanisms responsible for these findings are only now being explored, it is expected that a greater understanding of the roles played by TPO in HSC physiology will lead to novel therapeutic opportunities.
authors.affiliation: Department of Medicine, University of California, San Diego, San Diego, California 92103, USA. kkaushansky@ucsd.edu
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kaushansky
mesh_terms: D000818:Animals; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D053628:Receptors, Thrombopoietin; D033581:Stem Cell Transplantation; D034061:Thrombopoiesis; D013926:Thrombopoietin / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D013926:Thrombopoietin