EFFECTS OF TUMOR-NECROSIS-FACTOR-ALPHA ON BONE-MARROW ASPIRATES OF PATIENTS WITH ACUTE MYELOGENOUS LEUKEMIA DETERMINED BY FLOW-CYTOMETRIC CELL-CYCLE ANALYSIS

Tumour necrosis factor-alpha (TNF-alpha) exerts cytotoxic and antiproliferative effects on neoplastic cells. It has been used as a therapeutic agent for solid tumours and haematological malignancies. We report on the ex vivo determination of the effect of recombinant human rhuTNF-alpha on bone marrow aspirates by a bromodeoxyuridine/propidium iodide method. Cell samples were drawn after 0.5, 2, 4, 6, 8, 10, 22, and 25 h from short-term suspension bone marrow cultures from patients with acute myelogenous leukemia (AML). Flow-cytometric cell-cycle analysis was performed after double DNA staining with propidium iodide and anti-BrdU antibodies. By this method the effect of rhuTNF-alpha on cell proliferation can be evaluated after only 35 h. In about two-thirds of the bone marrow aspirates of AML an inhibiting effect on rhuTNF-alpha can be demonstrated, developing to its full extent after 10 h.