TNF receptors in chronic lymphocytic leukemia

Abstract

Two transmembrane receptors for tumor necrosis factor (TNF) with different molecular weight, 55 kD (p55) and 75 kD (p75), have been identified. In addition, the extracellular part of both receptors are shedded by proteolytic cleavage and exist as soluble receptors which bind to TNF in plasma and other biological fluids. Normal B cells produce TNF and express TNF receptors (R), mainly p75, upon stimulation. TNF costimulates DNA synthesis via the p75 receptor in normal B cells. The B cells from patients with chronic lymphocytic leukemia (CLL) produce TNF and have the capacity to express both receptor types. Also in malignant B cells the p75 receptor is dominant. TNF induce DNA synthesis in CLL cells via both receptors. CLL patients have elevated serum levels of soluble (s) TNFR and this is more pronounced in advanced disease. In conclusion, there is considerable support for TNF as an autocrine growth factor in CLL. However, the net effect of TNF is determined by the quantitative relationship between TNFR on the cell surface, TNF in plasma and sTNFR in plasma, and the affinities between TNF-p55 and TNF-p75. Due to increasing serum levels of sTNFR the significance of TNF as a growth factor is probably less important in advanced disease.