TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) AND LEUKEMIC-CELLS - SECRETION AND RESPONSE

Leukaemic cells from various types (ALL-0, ALL-proB, ALL-common [cALL] , ALL-T) of acute lymphoblastic leukaemia (ALL) and non-lymphoblastic leukaemia (ANLL) were studied for their ability to produce tumour necr osis factor alpha (TNF). The role of exogenous and endogenous TNF in p roliferation in vitro of leukaemic cells was also assessed. Leukaemic cells from different types of acute leukaemia were found to show major differences in their ability to proliferate in vitro. High production of TNF was observed mainly in ALL-T and ANLL but in ALL-T it was not associated with the proliferation rate of leukaemic cells. In most ins tances no bioactive TNF was detected. The variable response of leukaem ic cells (inhibition or stimulation of proliferation) to exogenous hum an recombinant (rTNF) was assessed. The role of endogenous TNF as a gr owth factor or agent associated with resistance to exogenous TNF was e xcluded as judged by a lack of effect of the TNF synthesis inhibitor p entoxifylline (PTX) and of anti-TNF antibody and PTX/rTNF. There was n o association of the effect of rTNF on proliferation of leukaemic cell s with their immunophenotype, spontaneous release of TNF or proliferat ion rate, Hence, this study does not provide evidence for the role of TNF as a growth factor for leukaemic cells or for its role in the inhi bition of proliferation of leukaemic cells.