Tumor necrosis factor induces proliferation of neoplastic B cells from chronic lymphocytic leukemia

Abstract

The biologic effects of recombinant tumor necrosis factor-alpha (rTNF- alpha) and the expression of specific TNF membrane receptors on isolated neoplastic B cells from previously untreated patients with chronic lymphocytic leukemia (CLL) were investigated in vitro. Isolated B cells were incubated up to six days with various concentrations of rTNF-alpha (0.1 to 100 ng/mL). B cells from most patients proliferated ranged from two to 104 times that of unstimulated cells from the same patients. An optimal proliferative effect was achieved at 25 ng/mL rTNF- alpha and an incubation time between 96 and 120 hours, whereas a low concentration of rTNF-alpha (1 ng/mL) reduced [3H]TdR incorporation in four cases. Metaphase cells were detected in the rTNF-alpha-stimulated cultures that proliferated in response to rTNF-alpha. B cells from three of ten patients proliferated spontaneously and proliferation was further enhanced in two patients by rTNF-alpha. TNF binding assays gave a value of approximately 390 to 1,400 binding sites/cell for TNF and a dissociation constant (kd) of approximately 60 pmol/L. These data indicate that rTNF-alpha, in contrast to its cytotoxic/cytostatic effects, can also induce proliferation of tumor cells.

ELEVATED CIRCULATING LEVELS OF TNFα AND ITS p55 SOLUBLE RECEPTOR ARE ASSOCIATED WITH AN ADVERSE PROGNOSIS IN LYMPHOMA PATIENTS

“…It has been reported recently that TNF can promote the growth of hairy cell leukaemia and chronic lymphocytic leukaemia cells, both tumour types derived from the B-cell compartment (Cordingley et al, 1988;Digel et al, 1989). Furthermore, several cytokines have recently been shown to play important roles in chronic lymphocytic leukaemia (Hoffbrand et al, 1993).…”

Serum level of soluble tumor necrosis factor receptor 2 is associated with the outcome of patients with diffuse large B‐cell lymphoma treated with the R‐CHOP regimen

“…After performing clinical analyses on the prognostic factors, some investigators suggested that serum levels of cytokines and their soluble receptors may reflect tumor growth and host tumor responses. TNF and its receptors are believed to be important in the growth, differentiation, and/or apoptosis of malignant cells in chronic lymphocytic leukemia (30), hairycell leukemia (31), Hodgkin's lymphoma, and NHL (32). Two different types of TNF receptors have been identified, the 55 kDa molecule (p55, TNFR; TNF-R1), and the 75 kDa molecule (p75, TNFR; TNF-R2).…”

CD40 regulation of death domains containing receptors and their ligands on lymphoma B cells

“…Several observations indicate that this up-regulation may not lead necessarily to apoptosis. In fact, TNF has been shown to induce B-cell proliferation in some models (Digel et al, 1989) and soluble human recombinant TNF did not TRAIL transcript is present in five FL samples. (b) Then three samples of purified FL cells were seeded in culture with medium alone (M), control untransfected fibroblastic layer (C) and human CD40L transfected fibroblastic layer (CD40L) with anti-CD40L mAb (Ab) or control IgG (cIg).…”