EFFECTS OF RECOMBINANT HUMAN THROMBOPOIETIN ON MEGAKARYOCYTE COLONY FORMATION AND MEGAKARYOCYTE PLOIDY BY HUMAN CD34(-FREE SYSTEM() CELLS IN A SERUM)

In serum-free cultures of human CD34 cells, recombinant human thrombop oietin (TPO) induced megakaryocyte colony formation in a dose-dependen t fashion that was further enhanced by the presence of interleukin-3 ( IL-3) and stem cell factor (SCF), but not by IL-6, IL-11 or erythropoi etin. TPO gave rise to much smaller colonies and at an earlier time th an IL-3, indicating that TPO affects predominantly more mature megakar yocytic progenitors. In liquid cultures, TPO increased the percentage and the absolute number of greater than or equal to 8N megakaryocytes, but it did not shift their modal ploidy from 2N. TPO-induced endomito sis was totally inhibited by the presence of, or previous exposure of cells to, IL-3 and/or SCF. The mechanism by which TPO overcomes in viv o the negative effects of IL-3 and SCF on megakaryocyte ploidy remains unknown.