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

  • Bruserud
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Abstract

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. © 2001 Elsevier Science B.V. All rights reserved.

Author-supplied keywords

  • Acute myelogenous leukemia
  • Fluconazole
  • Itraconazole
  • Ketoconazole
  • Miconazole
  • T lymphocytes

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  • Bruserud

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