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Expression and functional role of tumor necrosis factor receptors on
leukemic cells from patients with type B chronic lymphoproliferative
disorders
L Trentin, R Zambello, C Agostini, F Siviero, F Adami, R Marcolongo, R Raimondi, T Chisesi, G Pizzolo and G Semenzato
Department of Clinical Medicine, Padua University School of Medicine,
Padova, Italy.
Two receptors for tumor necrosis factor (TNF) with different molecular
weight (75-Kd and 55-Kd) and binding affinity have been recently
discovered. To investigate the distribution and the functional role of
these receptors on leukemic B cells from hairy cell leukemia (HCL) and
B-cell chronic lymphocytic leukemia (B-CLL) patients, we evaluated: (1) the
cytofluorimetric pattern of uncultured and cultured leukemic B cells
incubated with utr-1 and htr-9 monoclonal antibodies (MoAbs), which
specifically recognize the 75-Kd and 55-Kd TNF receptors (TNFR),
respectively; (2) the effect of TNF-alpha and TNF-beta on leukemic B cells
in an in vitro proliferation assay; (3) the role of anti-TNFR MoAbs on
TNF-alpha and TNF-beta-driven B-cell growth; and (4) the proliferative
effect of utr-1 and htr-9 MoAbs on in vitro cultured leukemic cells. Our
study shows that the high affinity (75-Kd) but not the low affinity (55-Kd)
TNFR molecules are expressed on freshly isolated leukemic B cells recovered
from HCL and B-CLL patients. The expression of these receptors was neither
upregulated nor downregulated by different stimuli, including TNF-alpha,
TNF-beta, B-cell growth factor, and interleukin-2. TNF-alpha efficiently
triggers the proliferation of HC and, to a lesser extent, the growth of
B-CLL cells. TNF-beta was also able to transduce the proliferative signal
in HCL, but not in B-CLL patients. TNF-alpha- and TNF-beta-driven B-cell
proliferation was inhibited by the preincubation of leukemic B cells with
utr-1 but not htr-9 MoAb. Moreover, anti-75-Kd, but not anti-55-Kd TNFR
MoAb, was able to trigger the proliferation of leukemic B cells, and in
particular of HC. These results show that leukemic B cells from patients
with HCL and B-CLL are equipped with a fully functional high affinity TNFR.
Volume 81,
Issue 3,
pp. 752-758,
02/01/1993
Copyright © 1993 by The American Society of Hematology

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