Apoptosis Susceptibility and Cell-Cycle Distribution in Cells from Myelodysplastic Syndrome Patients: Modulatory In-Vitro Effects of G-CSF and Interferon-α

Susceptibility to apoptosis varies in different forms of myelodysplastic syndromes (MDS). Our in vitro study aimed at better defining the cell kinetic profile by investigating whether G-CSF and interferon-α (IFNα) were capable of controling apoptotic/proliferative mechanisms in RAEB as well as in RAEB-t forms. Apoptosis and cell-cycle distribution were measured in mononuclear and in CD34+ cells from bone marrow samples of 27 MDS patients with RAEB (n = 15) and RAEB-t (n= 12). In selected samples, the in vitro influence of G-CSF and lymphoblastoid (Ly)-IFNα on the apoptotic susceptibility and on the cell kinetics of the above MDS populations was evaluated. RAEB samples showed a significantly greater apoptosis than RAEB-t ones, both in mononuclear cells (14.76% ′ 8.73 vs. 5.95% ′ 3.88, P = 0.0058) and in CD34+ cells (24.66% ′ 16.08 vs. 3.96% ′ 2.57, P = 0.0007). Short-term cell culture in the presence of G-CSF reduced apoptosis in CD34+ cells in all 4 RAEB samples tested (39.1% ′ 40.7 vs. 21.0% ′ 23.5, P = n.s.); the percentage of cells in S-phase significantly increased in 3/4 samples (19.90% ′ 4.40 vs. 32.40% ′ 7.85, P = 0.03). Ly-IFNa protected CD34+ cells from apoptosis in 3/4 RAEB samples (25.7% ′ 8.06 vs. 10.9% ′ 8.8, P = n.s.), but did not modulate cell-cycle distribution. G-CSF and Ly-IFNα failed to affect apoptosis and proliferation in RAEB-t. These observations indicate that in RAEB forms increased apoptosis can be efficiently counteracted in most of the samples by both G-CSF and Ly-IFNα, suggesting that only in these forms a retained regulatory mechanism on the apoptotic/ proliferative balance may allow therapeutic intervention with apoptotic regulators.