Dose-response relationship of megakaryocyte progenitors from the bone marrow of thrombocytopenic and non-thrombocytopenic neonates to recombinant thrombopoietin

Megakaryocyte (MK) progenitors from the marrow of adults undergo dose-depen dent clonogenic proliferation in response to recombinant thrombopoietin (rT po). It is unknown whether progenitors from the marrow of thrombocytopenic neonates display rTpo dose-dependent proliferation and whether they are mor e or less sensitive to rTpo than progenitors from non-thrombocytopenic neon ates or adults. To assess this, we cultured marrow from four thrombocytopen ic and four non-thrombocytopenic neonates, and from six healthy adults, in a serum-free system in the presence of increasing concentrations of rTpo (0 -100 ng/ml). Marrow from the thrombocytopenic and non-thrombocytopenic neon ates generated three times more MK colonies/10(5) light density cells (129 +/- 39 and 167 +/- 30 respectively) than marrow from adults (54 +/- 30, P < 0.0001) at a rTpo concentration of 50 ng/ml. Neonatal and adult samples ha d a rTpo dose-dependent increase in MK colonies. However, neonates reached a maximal number of colonies at a rTpo concentration of 10 ng/ml, compared with 50 ng/ml in adults, resulting in a larger area under the rTpo dose-res ponse curve for neonatal progenitors (P = 0.0047). Neonates also generated more large MK colonies than the adults (24% vs. 2% at 100 ng/ml).