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.
Tumor necrosis factor induces proliferation of neoplastic B cells from chronic lymphocytic leukemia
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W Digel, M Stefanic, W Schoniger, C Buck, A Raghavachar, N Frickhofen, H Heimpel, F Porzsolt; Tumor necrosis factor induces proliferation of neoplastic B cells from chronic lymphocytic leukemia. Blood 1989; 73 (5): 1242–1246. doi: https://doi.org/10.1182/blood.V73.5.1242.bloodjournal7351242
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