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

Abstract

The biologic effects of recombinant tumor necrosis factor-a (rTNF-a) 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-a (0.1 to 100 ng/mL). B cells from most patients proliferated in a dose-dependent manner. The rate of proliferation 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-a and an incubation time between 96 and 120 hours, whereas a low concentration of rTNF-a (1 ng/mL) reduced [3H]TdR incorporation in four cases. Metaphase cells were detected in the rTNF-a-stimulated cultures that proliferated in response to rTNF-a. B cells from three of ten patients proliferated spontaneously and proliferation was further enhanced in two patients by rTNF-a. TNF binding assays gave a value of ~ 390 to 1,400 binding sites/cell for TNF and a dissociation constant (kd) of ~ 60 pmol/L. These data indicate that rTNF-a, in contrast to its cytotoxic/cytostatic effects, can also induce proliferation of tumor cells.