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Thursday 01 November 2001

Effects of azoles on human acute myelogenous leukemia blasts and T lymphocytes derived from acute leukemia patients with chemotherapy-induced cytopenia.

By: Bruserud O.

Int Immunopharmacol 2001 Nov;1(12):2183-95

The effects of azoles (fluconazole, ketoconazole, miconazole, itraconazole) on human acute myelogenous leukemia (AML) blasts and T lymphocytes were studied in vitro. All the azoles altered spontaneous proliferation, cytokine-dependent proliferation and constitutive cytokine secretion by native AML blasts for a subset of patients, and all the drugs then had divergent effects. All four drugs also affected the responsiveness (cytokine-dependent and mitogen-stimulated proliferation, cytokine release) of clonogenic CD4+ and CD8+ T cells derived from acute leukemia patients with chemotherapy-induced cytopenia. However, the T cell effects were also divergent and dependent on differences between various azoles, AML accessory cells and mitogenic activation signals. These drug effects may have a clinical relevance in acute leukemia patients receiving intensive chemotherapy together with azoles as prophylaxis or treatment for fungal infections: (i) effects on AML blasts may influence their susceptibility to drug-induced apoptosis; and (ii) effects on T cells may alter effector functions that mediate additional antileukemic effects in patients receiving intensive chemotherapy.

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