Hypersensitivity of megakaryocyte progenitors to thrombopoietin in essential thrombocythemia

Essential thrombocythemia (ET) is a clonal myeloproliferative disorder char acterized by an elevation of platelets in peripheral blood and excessive pr oliferation of megakaryocytes in bone marrow. The pathological mechanisms f or the elevation of megakaryocytes and platelets in ET remain unclear. To s tudy the hypersensitivity of megakaryocyte progenitors to thrombopoietin (T PO), a 9-year-old girl, diagnosed with ET, underwent dose-response experime nts with recombinant human TPO, using her bone marrow nonadherent mononucle ar cells and CD34 positive cells. Spontaneous colony-forming unit-megakaryo cytes (CFU-Meg) were observed in serum-deprived cultures of non-adherent mo nonuclear cells, whereas they disappeared in cultures of CD34 positive cell s. The patient's CFU-Meg showed maximal growth at concentrations of TPO low er than those for normal children. Dose-response curves demonstrated a 50-8 0 fold increase In sensitivity of the patient's CFU-Meg to TPO. We observed hypersensitivity of megakaryocyte progenitors to TPO in a child with ET. O ur results suggest that spontaneous CFU-Meg formation in patients with ET m ay be due to hypersensitivity to TPO. (C) 2001 Wiley-Liss, Inc.