Effects of azoles on human acute myelogenous leukemia blasts and T lymphocytes derived from acute leukemia patients with chemotherapy-induced cytopenia.
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.
Bruserud
O
O
Department of Medicine, Haukeland University Hospital and the University of Bergen, Norway. oystein.bruserud@haukeland.no
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D015725:Fluconazole / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D017964:Itraconazole / Q000494:pharmacology*; D007654:Ketoconazole / Q000494:pharmacology*; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000473:pathology*; D007970:Leukopenia / Q000097:blood / Q000139:chemically induced*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008825:Miconazole / Q000494:pharmacology*; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D000935:Antifungal Agents; D015847:Interleukin-4; D017964:Itraconazole; D008825:Miconazole; D007371:Interferon-gamma; D015725:Fluconazole; D007654:Ketoconazole