In the 1990s it was known that thrombopoietin (TPO) stimulates megakaryocyte production both in vitro and in vivo [1-3]. Size, number, and mean geometric ploidy of megakaryocytes are much more increased by TPO as compared with other cytokines with thrombopoietic activity. Evidence for a decisive role of deregulated TPO in ET comes from observations in mice overexpressing a TPO transgene where increased TPO production resulted in a fatal myeloproliferative disorder . High dose exposure to TPO, lethally irradiated mice grafted with bone marrow cells infected with a retrovirus carrying the murin TPO cDNA (TPOhigh mice) developed a lethal myeloproliferative disorder of TPO induced megakaryocytic myeloproliferation (Figure 1 and 2) with reduced erythropoiesis in the spleen and bone marrow [5,6]. Transient myelofibrosis is observed in rats receiving recombinant TPO .