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.

journal_name

Ann N Y Acad Sci

authors

Kaushansky K

doi

10.1111/j.1749-6632.2003.tb03230.x

subject

Has Abstract

pub_date

2003-05-01 00:00:00

pages

39-43

eissn

0077-8923

issn

1749-6632

journal_volume

996

pub_type

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