In-vitro treatment of B-chronic lymphocytic leukaemia (B-CLL) cells with tumour necrosis factor (TNF) induced the transcription of the proto-oncogenes c-fos, c-jun and c-myc. The products of these oncogenes appear to be involved in the signal transmission initiated via the phosphoinositol lipid and protein kinase C (PKC) signal transduction pathway. In contrast to the rapid induction of these oncogene products by the phorbol ester TPA (which directly activates PKC) alone or in combination with the calcium ionophore A23187, stimulation of c-fos, c-jun and c-myc mRNA expression by TNF is significantly delayed. A later onset of action mediated by TNF has similarly been reported for the induction of DNA synthesis and of gene expression following gene transfer in B-CLL cells. The delay in the response of B-CLL cells to TNF might be due to the delayed stimulation of the oncogene signal transmitters fos, jun and myc by TNF. The mechanism for this delay remains to be elucidated.
Keywords: B-CLL; TNF; c-onc.