Thrombopoietin: basic biology, clinical promise

Cytokines which regulate thrombopoiesis have been the subject of intense study and debate over the past 35 years. Recently, based on recognition of the orphan cytokine receptor c-mpl, thrombopoietin (Tpo), the primary regulator of platelet production has been cloned. Its biological properties form the basis of this review. Tpo promotes both the proliferation of megakaryocytic progenitor cells and their maturation into platelet-producing megakaryocytes. It acts to expand megakaryocyte size and ploidy, and increases the expression of platelet-specific membrane glycoproteins. In vivo, Tpo greatly augments marrow and splenic megakaryocytic progenitor cells and large megakaryocytes, and leads to profound increases in platelet production. In addition, the hormone hastens the recovery or platelet counts following cytoreductive therapies, and has been associated with improved survival in certain murine models. Clearly, our growing understanding of the biology or Tpo will lead to important new insights into megakaryopoiesis, and to clinical improvements in the therapy of both natural and acquired states of marrow failure.