Tumour necrosis factor alpha (TNF alpha) and leukaemic cells: secretion and response.

Leukaemic cells from various types (ALL-O, 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 necrosis factor alpha (TNF). The role of exogenous and endogenous TNF in proliferation 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 instances no bioactive TNF was detected. The variable response of leukaemic cells (inhibition or stimulation of proliferation) to exogenous human recombinant (rTNF) was assessed. The role of endogenous TNF as a growth factor or agent associated with resistance to exogenous TNF was excluded as judged by a lack of effect of the TNF synthesis inhibitor pentoxifylline (PTX) and of anti-TNF antibody and PTX/rTNF. There was no association of the effect of rTNF on proliferation of leukaemic cells with their immunophenotype, spontaneous release of TNF or proliferation 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 inhibition of proliferation of leukaemic cells.