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.
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Authors | Kenneth Kaushansky |
Journal | Annals of the New York Academy of Sciences
(Ann N Y Acad Sci)
Vol. 996
Pg. 39-43
(May 2003)
ISSN: 0077-8923 [Print] United States |
PMID | 12799280
(Publication Type: Journal Article)
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Chemical References |
- Neoplasm Proteins
- Proto-Oncogene Proteins
- Receptors, Cytokine
- Receptors, Thrombopoietin
- MPL protein, human
- Thrombopoietin
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Topics |
- Animals
- Hematopoietic Stem Cells
(cytology, metabolism)
- Humans
- Mice
- Neoplasm Proteins
(metabolism)
- Proto-Oncogene Proteins
(metabolism)
- Receptors, Cytokine
(metabolism)
- Receptors, Thrombopoietin
- Stem Cell Transplantation
- Thrombopoiesis
- Thrombopoietin
(metabolism)
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