THROMBOPOIETIN STIMULATES MYELODYSPLASTIC SYNDROME GRANULOCYTE-MACROPHAGE AND ERYTHROID PROGENITOR PROLIFERATION

Thrombopoietin (TPO) has been successfully used to stimulate megakaryo cyte progenitor proliferation and platelet production both in vitro an d in vivo. We and other investigators have found that TPO also stimula tes normal marrow colony-forming unit, granulocyte-macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-E) growth. In contrast to its e ffect on normal marrow precursors, TPO stimulates acute myelogenous le ukemia (AML) progenitor proliferation in only 25% of the cases. Becaus e the hematopoietic cells in Myelodysplastic syndrome (MDS) originate from both the normal and leukemic clones, we hypothesized that TPO may be a useful therapeutic agent for MDS. To test this hypothesis, we us ed fresh marrow samples taken from 14 MDS patients. We found that in t he presence of fetal calf serum (FCS) and erythropoietin (EPO) TPO (5 to 40 ng/ml) MDS CFU-GM and BFU-E colony-forming cell proliferation we re stimulated in a dose-dependent fashion by up to 103% and 93% respec tively. This effect was similar to the stimulation obtained with optim al concentrations of granulocyte colony-stimulating factor (G-CSF), gr anulocyte-macrophage CSF (GMCSF), or interleukin-3 (IL-3). Furthermore , TPO increased the colony-stimulatory effects of G-CSF, GM-CSF,IL-3,a nd stem cell factor (SCF) on MDS marrow cells. However, depletion of e ither T lymphocytes or adherent cells abrogated the effect of TPO, sug gesting that the effect is not a direct one but is mediated through in teraction with cytokines produced by accessory cells. Taken together, our data suggest that the therapeutic role of TPO in the management of MDS warrants further investigation.