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Expression and regulation of tumor necrosis factor, interleukin-2, and
hematopoietic growth factor receptors in B-cell chronic lymphocytic
leukemia
L Trentin, R Zambello, C Agostini, C Enthammer, A Cerutti, F Adami, S Zamboni and G Semenzato
Padua University School of Medicine, Department of Clinical Medicine,
Italy.
Leukemic cells from patients with B-cell chronic lymphocytic leukemia
(B-CLL) express tumor necrosis factor (TNF) and interleukin-2 (IL-2)
receptors, but only a low proliferative response can be elicited in vitro
by TNF alpha and IL-2. To investigate the functional properties of IL-2 and
TNF alpha on leukemic B cells, we evaluated (1) the regulation of
expression of TNF receptors (TNF-R) and IL-2 receptors on leukemic B cells
after culture with TNF alpha and IL-2; (2) the effect of the combination of
TNF alpha and IL-2 in a proliferative in vitro assay; and (3) the
expression and regulation by these cytokines of receptors for hematopoietic
factors, including IL-3, granulocyte colony- stimulating factor (G-CSF),
and granulocyte-macrophage colony- stimulating factor (GM-CSF). Flow
cytometry analysis showed that freshly isolated leukemic cells from B-CLL
patients bear the 75-kD TNF- R and the 55-kD IL-2R; TNF alpha was able to
upregulate the 55-kD IL-2R but not the 75-kD TNF-R. On the other hand, IL-2
was not able to modify the expression of the above-mentioned receptors.
Although each cytokine alone was unable to induce a relevant proliferation
of leukemic cells, a synergistic proliferative effect was detected when
these cytokines were used in combination. Leukemic B cells from B-CLL
patients bear receptors for hematopoietic factors (IL-3, G-CSF, and GM-CSF)
that were upregulated in vitro by IL-2 via the 55-kD IL-2R. On the
contrary, TNF alpha was unable to affect the expression of the
above-mentioned receptors. These results indicate (1) that IL-2 and TNF
receptors are related to each other on leukemic cells in B-CLL and (2) that
the IL-2R is involved in the regulation of other structures, ie, CSF
receptors, thus pointing to another functional role of this receptor
complex and the related cytokine in leukemic cells.
Volume 84,
Issue 12,
pp. 4249-4256,
12/15/1994
Copyright © 1994 by The American Society of Hematology
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