EFFECTS OF TUMOR-NECROSIS-FACTOR ON PRIMARY HUMAN LEUKEMIA-CELLS - ULTRASTRUCTURAL-CHANGES

We investigated the ultrastructural effects of recombinant tumor necro sis factor a (TNF) on primary leukemia cells of 8 patients (4 cases of acute myelogenous leukemia and 4 cases of chronic myelogenous leukemi a) as well as on bone marrow cells of 1 normal control. The cells were kept in liquid culture for up to 92 h in the presence of up to 10,000 U/ml of recombinant human TNF without adding colony-stimulating facto rs. Under these conditions the concentration of viable leukemic cells decreased by 14 to 53%, compared to control cultures. In acute myeloge nous leukemia, all cases to some degree developed an enlargement of mi tochondria; in 2 cases prominent cytoplasmic processes, and in 2 cases cytoplasmic vacuoles were observed. In chronic myelogenous leukemia, an enlargement and deformation of all cell types was observed to varyi ng degrees. In the normal bone marrow sample only minor cytoplasmic ch anges occurred. In all cultures apoptotic changes were rarely observed and - if present - were observed also in cultures without TNF. When t he DNA of leukemic cells treated with TNF was separated on agarose, no fragments characteristic of apoptosis were visible. Our results demon strate that TNF does not induce direct cytotoxicity or apoptosis in ac ute or chronic myeloid leukemias and are compatible with the notion th at some leukemic cells may be activated or stimulated by TNF. The mito chondrion appears to be one of the primary targets of TNF. Electron mi croscopy is useful for monitoring the changes induced by TNF.