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-dependent clonogenic proliferation in response to recombinant thrombopoietin (rTpo). It is unknown whether progenitors from the marrow of thrombocytopenic neonates display rTpo dose-dependent proliferation and whether they are more or less sensitive to rTpo than progenitors from non-thrombocytopenic neonates or adults. To assess this, we cultured marrow from four thrombocytopenic 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 neonates generated three times more MK colonies/10⁵ 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 had 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-response curve for neonatal progenitors (P = 0·0047). Neonates also generated more large MK colonies than the adults (24% vs. 2% at 100 ng/ml).