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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Antineoplastic Agents, Arabinonucleosides, Cell Line, Tumor, Cell Proliferation, Drug Resistance, Multiple, Drug Resistance, Neoplasm, HL-60 Cells, Humans, Lymphoma, B-Cell, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Purine Nucleosides, Purine-Nucleoside Phosphorylase, Pyrimidinones.
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Is a nelarabine-resistant T-lymphoblastic leukemia CCRF-CEM variant cell line cross-resistant to the purine nucleoside phosphorylase inhibitor forodesine? Context: Forodesine inhibits purine nucleoside phosphorylase, resulting in an accumulation of intracellular dGTP and consequently cell death. 9-β-D-Arabinofuranosylguanine (ara-G) is an active compound of nelarabine that is intracellularly phosphorylated to a triphosphate form, which inhibits DNA synthesis. Both agents show cytotoxicity toward T-cell malignancies. In the present study, we investigated the cytotoxicity of forodesine in vitro using ara-G-resistant leukemia cells. T-Lymphoblastic leukemia cell line CCRF-CEM and ara-G-resistant CEM variant cell line CEM/ara-G that we had previously established were used. A growth-inhibition assay demonstrated that CEM cells were insensitive to single-agent forodesine treatment. The cells were also insensitive to deoxyguanosine at a maximal concentration of 10 μM. CEM/ara-G cells were 80-fold more resistant to ara-G than were CEM cells, and the mode of sensitivity to forodesine and deoxyguanosine was similar to that of CEM cells. In the presence of 10 μM deoxyguanosine, forodesine effectively inhibited the growth of CEM cells but not that of CEM/ara-G cells. Flow cytometric analyses showed that combination of forodesine and deoxyguanosine induced apoptosis of CEM cells but not of CEM/ara-G cells. The addition of ara-G did not augment the cytotoxicity of the forodesine/deoxyguanosine combination towards CEM cells or CEM/ara-G cells. The combination index revealed antagonism between forodesine and ara-G. The intracellular production of ara-G triphosphate was reduced in the presence of forodesine.
assistant
Nelarabine-resistant CEM/ara-G cells are insensitive to forodesine. Final Decision: yes