Megakaryocytes: Their precursors and their progeny

Although first defined nearly 40 years ago, the existence of thrombopoietin, the primary regulator of megakaryocyte and platelet production, was in doubt until only very recently. Since the initial reports of its cloning in 1994, much has been learned about the effects of the hormone on megakaryocytic proliferation and differentiation. Thrombopoietin affects all aspects of megakaryocyte development, from the commitment of hematopoietic stem cells to the megakaryocytic lineage through their maturation into large highly polyploid cells capable of fragmentation into thousands of platelets. As such, recombinant thrombopoietin will undoubtedly find use to augment platelet production in states of impaired bone marrow function. Moreover, as a number of pathologic states of platelet production are associated with abnormalities of homeostasis or thrombosis, a better comprehension of the mechanisms by which platelets are derived from marrow megakaryocytes will likely aid in our approach to a number of cardiovascular disorders. The availability of thrombopoietin ushers in a new era of understanding of the physiology of megakaryocytes, their precursors, and their progeny.