Abstract
Essential thrombocythemia (ET) is a clonal myeloproliferative disorder of unknown origin primarily involving the megakaryocyte/platelet lineage. In an attempt to evaluate the role of the receptor c-mpl and its ligand thrombopoietin (TPO) in ET, various studies have been undertaken, the results of which are discussed herein. Normal or even elevated TPO levels in ET despite an increased megakaryocyte/platelet mass suggest abnormal feedback mechanisms in the regulation of TPO production and consumption. Deregulated levels of TPO in the circulation of patients with ET may be the result of an abnormal TPO consumption by platelets and megakaryocytes. It has been shown that proto-oncogene c-mpl is involved in spontaneous megakaryopoiesis in myeloproliferative disorders. Evidence for a decisive role of deregulated TPO in ET also comes from observations in mice overexpressing a TPO transgene where increased TPO production has resulted in a fatal myeloproliferative syndrome. Future research will study quantitative and qualitative deficiencies of c-mpl, the kinetics of the interaction of c-mpl with its ligand (TPO), and the role of autocrine or paracrine production of c-mpl ligand in increasing megakaryopoiesis so as to further elucidate its pathobiologic significance in ET.
Keywords:
Essential thrombocythemia - pathobiology - thrombopoietin - c-mpl receptor
