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Interleukin-15 promotes the growth of leukemic cells of patients with B-
cell chronic lymphoproliferative disorders
L Trentin, A Cerutti, R Zambello, R Sancretta, C Tassinari, M Facco, F Adami, F Rodeghiero, C Agostini and G Semenzato
Department of Clinical and Experimental Medicine, Padua University School
of Medicine, Padova, Italy.
The recently discovered cytokine, interleukin-15 (IL-15), has been
demonstrated to share several biologic properties with IL-2 in different
cell systems, including T-cell and natural killer (NK) cell compartments.
As for B lymphocytes, IL-15 has been shown to provide stimulatory
activities in normal preactivated B cells that are mainly transduced
through IL- 2 receptor (IL-2R) complex components. Since leukemic B cells
from patients with chronic lymphoproliferative disorders (CLD) bear IL-2R
and grow in response to IL-2, we investigated whether IL-15 triggers the
proliferation of malignant B cells obtained from 12 patients with B-cell
chronic lymphocytic leukemia (B-CLL) and five patients with hairy cell
leukemia (HCL). Enriched B cells recovered from five healthy subjects were
also studied as controls. IL-15 stimulated the proliferation of freshly
isolated leukemic B cells, but not resting normal B lymphocytes, the latter
being able to grow in the presence of IL-15 only after in vitro
preactivation with phorbol myristate acetate. The proliferation elicited by
IL-2 on leukemic cells was comparable to that determined by IL-15.
Following addition of graded concentrations of IL-15 to
low/intermediate-dose IL-2, resting leukemic B cells showed a higher
stimulatory rate than that observed using the two cytokines separately. In
normal resting B lymphocytes, this cumulative effect was not observed. The
role of different IL-2R subunits in IL-15-driven growth of malignant B
cells was investigated both by their expression on leukemic cells and by
the block of different IL-2R subunits (p55, p75, and p64) with specific
monoclonal antibodies (MoAbs). Using flow cytometry and reverse
transcriptase-polymerase chain reaction (RT-PCR) analyses we demonstrated
that both B-CLL and HCL leukemic B cells express the beta and gamma chains
of the IL-2R system. The stimulatory activity achieved by IL-15 decreased
significantly, blocking the beta and gamma chains of the IL-2R. Taken
together, these findings demonstrate that IL-15 triggers the growth of
leukemic B cells through IL-2R system subunits, pointing to the role of
this novel cytokine in regulating the neoplastic proliferation in CLD.
Volume 87,
Issue 8,
pp. 3327-3335,
04/15/1996
Copyright © 1996 by The American Society of Hematology
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