Interleukin 3 protects murine bone marrow cells from apoptosis induced by DNA damaging agents

Chester Beatty Laboratories, Institute of Cancer Research, London, United Kingdom.
Journal of Experimental Medicine (Impact Factor: 13.91). 11/1992; 176(4):1043-51.
Source: PubMed

ABSTRACT Murine bone marrow-derived cells, dependent on interleukin 3 (IL-3) for their growth in culture, undergo programmed cell, or apoptosis, upon cytokine withdrawal. Here it is reported that a variety of DNA damaging agents cause a more rapid onset of apoptosis in a factor-dependent cell line, BAF3, deprived of IL-3. In contrast, when cultured in the presence of IL-3, or other growth promoting factors, BAF3 cells are highly resistant to X-irradiation and the cytotoxic drugs etoposide and cisplatin. Overexpression of the bcl2 gene product also protects BAF3 cells from DNA damage. The presence of IL-3 is not required during the initial events of DNA damage or its repair. In the absence of IL-3, cells still complete the repair of DNA breaks within 15 min, and continue to cycle for 5 h. At this time, IL-3 is necessary to prevent the accelerated onset of DNA cleavage from a G2 arrest point.

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    • "de la combinaison de cytokines 4F a été élaboré selon deux critères : facteurs de survie et d'expansion cellulaire (Borge et al. 1997; Brandt et al. 1994; Collins et al. 1992; Gratwohl et al. 1998; Keller et al. 1995; Kinoshita et al. 1995; Limanni et al. 1995; Leary et al. 1992; Neta 1997; Neta et al. 1993; Osada et al. 1999; Shah et al. 1996; Veiby et al. 1996). Le SCF et le FL ont été retenus comme facteurs de survie, l'IL-3 comme facteur d'expansion multilignage et la thrombopoïétine comme facteur mégacaryocytaire. "
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    • "The cause of the treatment resistance in most leukaemias remains a matter of intense investigation. Signals that block apoptosis are now well recognized to be important causes of resistance to anticancer drugs (Bedi et al, 1995; Steinmann et al, 1991; Lowe et al, 1993; Clark et al, 1993; McGahon et al, 1994; Miyashita & Reed, 1993; Strasser et al, 1991; Sentman et al, 1991; Collins et al, 1992); however, their role in acute leukaemia drug resistance has not been well studied. We found that enhanced survival of AML cells in serum-free medium, resulting from inhibited apoptosis, is associated with both in vitro and in vivo pan-resistance to cytotoxic anti-leukaemic therapy. "
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