Tumor necrosis factor modulates CD 20 expression on cells from chronic lymphocytic leukemia: A new role for TNF alpha?

Tumor necrosis factor alpha (TNF alpha) is a pleiotropic cytokine that is c onstitutively produced by leukemic cells in B Chronic Lymphocytic Leukemia (B-CLL). It has been shown to have autocrine and paracrine functions in nor mal B cells and in B lymphoproliferative diseases. This study was conducted to determine the effect of TNF alpha (in vitro) on CD20 expression on cell s from patients with B-CLL. Currently, anti-CD20 monoclonal antibody therap y is becoming a second line treatment in the management of B cell disorders like low-grade non-Hodgkin's lymphoma (NHL) and B-CLL. Our results demonst rate amply that very low doses of TNF alpha (0.0125 ng/ml) can be used to s ignificantly increase CD20 expression on cells from patients of B-CLL as ev idenced by increases in both percentage positivity and mean fluorescence in tensity. The upregulation is evident as early as 24 hours and is maintained for up to 72 hours. We propose that the upregulation is a direct result of in vitro differentiation stimulated by TNF alpha. The results presented ca n be exploited in the designing of priming protocols prior to antibody ther apy and this is discussed. (C) 2000 Wiley-Liss, Inc.