Apoptosis susceptibility and cell-cycle distribution in cells from myelodysplastic syndrome patients: modulatory in-vitro effects of G-CSF and interferon-alpha.

Abstract

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.

• Authors: Maria R Ricciardi, Maria T Petrucci, Chiara Gregorj, Vincenza Martini, Anna Levi, Maria R De Cuia, Roberto Latagliata, Maria C Petti, Franco Mandelli, Robin Foà, Agostino Tafuri
• Journal: Leukemia & lymphoma (Leuk Lymphoma) Vol. 45 Issue 7 Pg. 1437-43 (Jul 2004) ISSN: 1042-8194 [Print] United States
• PMID: 15359645 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interferon-alpha
• Granulocyte Colony-Stimulating Factor

Topics

• Adult
• Aged
• Anemia, Refractory, with Excess of Blasts (classification, pathology)
• Apoptosis (drug effects)
• Bone Marrow Cells (drug effects, pathology)
• Cell Cycle (drug effects)
• Cells, Cultured (cytology, drug effects)
• Female
• Granulocyte Colony-Stimulating Factor (pharmacology)
• Humans
• Interferon-alpha (pharmacology)
• Male
• Middle Aged