Tumor Necrosis Factor Production in B Cell Chronic Lymphocytic Leukemia

Tumor necrosis factor (TNF) has been suggested to act as an autocrine growth factor in chronic B cell malignancies. We have attempted to assess the role of TNFα in relation to the stage of chronic lymphocytic leukemia (CLL) by examining TNFα cytotoxic activity of media conditioned by stimulated and unstimulated peripheral blood mononuclear cells (PBMC) and by separated unstimulated malignant B cells from Rai stage 0 and IV patients. The response of PBMC from stage IV to stimulation with phytohemagglutinin, or bacterial lipopolysaccharide was weak or absent. However, stimulation of stage 0 PBMC induced significantly increased production of TNF. Furthermore, unstimulated stage 0 PBMC and B cells from these cases of stage 0 B CLL spontaneously released TNF in significant excess compared to normal PBMC controls while no TNF activity could be detected in supernatants from unstimulated stage IV PBMC or B cells. These data suggest a possible role for TNF in the progression of CLL.