Thrombopoietin, interleukin-11, and early-acting megakaryocyte growth factors in human myeloid leukemia cells

In this study we report our data on effects of early-acting megakaryocyte g rowth factors, particularly the c-mpl ligand also known as thrombopoietin ( TPO) and interleukin-11 (IL-11). on cell proliferation and apoptosis (Apo) of primary acute myeloid leukemia (AML) cells. A proliferative response to TPO was noticed in the majority of AML samples (17/19) with an average incr ease of S-phase cells from 7.8% +/- 1.5 to 14.5% +/-2.1 (p=0.0006). Resulti ng cell cycle activation did not always correlate with expression of the c- mpl receptor, although it was coupled, in the majority of samples, by an av erage decrease of apoptotic cells from 13% +/-0.7 to 8.8% +/-1.8 (p=0.05). Clonogenic cell growth (CFU-L) was confirmed in 5/17 of the samples with a mean colony number of 21.4 +/-9.6 x 10(5) cells plated. Conversely, effects of IL-11 on AML cells demonstrated that cell cycle changes: (recruitment f rom G(0) to S phase) were promoted only in a minority of samples (2/14) and there was little, if any, effect on CFU-L growth (mean colony number=17.5 +/-9.5) or Apo (from 13% +/-0.7 to 13.3+/-1.9). Combination of TPO with IL- 11 induced a slight increase of clonopenic cell growth, while the addition of IL-3 or SCF to the c-mpl ligand significantly raised the mean colony num bers up to 119.2 +/-68.3 and 52.9+/-22.1 x 10(5) cells plated, respectively . In summary, TPO shows activity on AML cells by stimulating their prolifer ation in a significant proportion of cases and generally protecting the maj ority of AML blast cells from induction of Apo. Conversely, IL-11 exerts li ttle effect on the cell cycle activation and Apo. These data help to unders tand regulation of myeloid leukemia cell growth and should be considered in the clinical use of early-acting megakaryocyte growth factors in acute leu kemia.