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

• Published in: Leukemia & lymphoma 2004-07, Vol.45 (7), p.1437-1443
• Main Authors: Ricciardi, Maria R, Petrucci, Maria T, Gregorj, Chiara, Martini, Vincenza, Levi, Anna, De Cuia, Maria R, Latagliata, Roberto, Petti, Maria C, Mandelli, Franco, Foà, Robin, Tafuri, Agostino
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anemia, Refractory, with Excess of Blasts - classification; Anemia, Refractory, with Excess of Blasts - pathology; Apoptosis; Apoptosis - drug effects; Bone Marrow Cells - drug effects; Bone Marrow Cells - pathology; Cell cycle; Cell Cycle - drug effects; Cells, Cultured - cytology; Cells, Cultured - drug effects; Female; G-CSF; Granulocyte Colony-Stimulating Factor - pharmacology; Humans; IFNα; Interferon-alpha - pharmacology; Male; Middle Aged; Myelodysplastic syndromes
• ISSN: 1042-8194; 1029-2403
• DOI: 10.1080/10428190310001657335

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-alpha (IFNalpha) 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)-IFNalpha 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-IFNalpha 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-IFNalpha 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-IFNalpha, suggesting that only in these forms a retained regulatory mechanism on the apoptotic/ proliferative balance may allow therapeutic intervention with apoptotic regulators.