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  • Title: Resistance of human leukemic cell lines to 1-beta-D-arabinofuranosylcytosine: characterization of an experimental model.
    Author: Gariboldi MB, Ravizza R, Marras E, Perletti G, De Simone A, Piccinini F, Monti E.
    Journal: Int J Oncol; 2001 Jun; 18(6):1245-9. PubMed ID: 11351258.
    Abstract:
    1-beta-D-arabinofuranosylcytosine (ara-C) is an antimetabolite used for the treatment of acute myelogenous leukemia. The ability of ara-C to kill neoplastic cells has been correlated to the induction of apoptosis. The clinical use of ara-C is limited by the development of drug resistance. Alterations in drug-induced apoptosis play a critical role in ara-C resistance. In particular, the proto-oncogene bcl-2 has been implicated in this phenomenon. To better understand the molecular basis of the role of bcl-2 in ara-C resistance, we investigated the relationship between the cytotoxic effect of ara-C, the expression levels and the subcellular localization of bcl-2 in three human leukemic cell lines (HL-60, KG1, J111). We have also evaluated the effects of ara-C on the J111 leukemic cell line (showing the lowest levels of Bcl-2 and the highest sensitivity to ara-C) overexpressing the bcl-2 oncogene. The model we developed here will allow further studies on the role of post-translational events involving bcl-2 (such as translocation and/or phosphorylation) in the cellular response to ara-C treatment.
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