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Tumor necrosis factor induces proliferation of neoplastic B cells from
chronic lymphocytic leukemia
W Digel, M Stefanic, W Schoniger, C Buck, A Raghavachar, N Frickhofen, H Heimpel and F Porzsolt
Department of Internal Medicine III, University of Ulm, FRG.
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.
Volume 73,
Issue 5,
pp. 1242-1246,
04/01/1989
Copyright © 1989 by The American Society of Hematology
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