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- Title
High susceptibility of human leukemic cells to Fas-induced apoptosis is restricted to G<sub>1</sub> phase of the cell cycle and can be increased by interferon treatment.
- Authors
Jedema, I; Barge, R M Y; Willemze, R; Falkenburg, J H F
- Abstract
In this study, we analyzed the influence of cell cycle status manipulations of leukemic cells on Fas-mediated apoptosis using the GM-CSF-dependent human myeloid leukemia cell line AML-193 as a model. GM-CSF and long-term treatment with interferon-gamma (IFN-γ) or interferon-alpha (IFN-α) were used to manipulate the cell cycle status. Control cells were GM-CSF deprived, nonproliferating cells. IFN-γ or IFN-α treatment did not induce proliferation in control cells, but resulted in recruitment of cells from resting Go phase into activated G[sub 1] phase. Using agonistic anti-Fas antibodies (FAS18), we demonstrated that this shift from G[sub 0] to G[sub 1] was accompanied by a 2.5-fold increase in Fas sensitivity. A similar increase in sensitivity to FAS18 could be obtained by induction of proliferation with GM-CSF. Quantitative FACS analysis of surviving cells after FAS18 induced apoptosis showed deletion of the G[sub 1] compartment, but complete protection of resting G[sub 0] cells. Cells in S or G[sub 2]/M phase were relatively protected against Fas induction. In conclusion, sensitivity to Fas-mediated apoptosis was restricted to cells in G[sub 1] phase of the cell cycle, and can be increased by treatment of cells with interferons. By this mechanism, interferon treatment may render leukemic cells more susceptible to lysis by T cells during immunotherapeutic interventions.
- Subjects
LEUKEMIA; INTERFERONS; IMMUNOTHERAPY
- Publication
Leukemia (08876924), 2003, Vol 17, Issue 3, p576
- ISSN
0887-6924
- Publication type
Article
- DOI
10.1038/sj.leu.2402844