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Hypersensitivity of megakaryocyte progenitors to thrombopoietin in essential thrombocythemia

H Kawasaki1, T Nakano, U Kohdera

  • 1Department of Pediatrics, Kansai Medical University, Moriguchi, Osaka, Japan. kawasaki@takii.kmu.ac.jp

American Journal of Hematology
|January 5, 2002
PubMed

Essential thrombocythemia (ET) is a clonal myeloproliferative disorder characterized by an elevation of platelets in peripheral blood and excessive proliferation of megakaryocytes in bone marrow. The pathological mechanisms for the elevation of megakaryocytes and platelets in ET remain unclear. To study the hypersensitivity of megakaryocyte progenitors to thrombopoietin (TPO), a 9-year-old girl, diagnosed with ET, underwent dose-response experiments with recombinant human TPO, using her bone marrow non-adherent mononuclear cells and CD34 positive cells. Spontaneous colony-forming unit-megakaryocytes (CFU-Meg) were observed in serum-deprived cultures of non-adherent mononuclear cells, whereas they disappeared in cultures of CD34 positive cells. The patient's CFU-Meg showed maximal growth at concentrations of TPO lower than those for normal children. Dose-response curves demonstrated a 50-80 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. Our results suggest that spontaneous CFU-Meg formation in patients with ET may be due to hypersensitivity to TPO.

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