Megakaryocytopoiesis: the state of the art

Megakaryocyte development and thrombopoiesis remain enigmatic processes, though less so than in the recent past. It is still virtually unknown how these cells acquire their signature characteristic, i.e. a hyperdiploid complement of DNA within a single nucleus. Why megakaryocytes become hyperdiploid at all also remains somewhat mysterious. Since the size of a megakaryocyte tends to correlate with the DNA content of its nucleus, it is assumed that development of hyperdiploidy allows these relatively rare cells to produce the large numbers of platelets that are required on a daily basis. Nevertheless, it has not been proven that higher ploidy cells produce more platelets than lower ploidy cells. The recent report of an in vitro assay for thrombopoiesis may allow this question to be addressed. Of greater significance, this past year has seen the cloning, and expression of the hormone thrombopoietin (TPO). This event clearly represents a major achievement in this area and which will hopefully assist in answering the fascinating biologic questions which remain unsolved in this area. It is also hoped that availability of recombinant TPO will prove to be of clinical utility as well. The following brief review attempts to summarize current perceptions about megakaryocyte developmental biology and the cloning of TPO.