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Chronic lymphocytic leukemia B cells are resistant to the apoptotic effects
of transforming growth factor-beta
RS Douglas, RJ Capocasale, RJ Lamb, PC Nowell and JS Moore
Department of Pathology and Laboratory Medicine, University of
Pennsylvania, Philadelphia 19104-6082, USA.
Chronic lymphocytic leukemia (CLL) is the most common leukemia of the
western world and is characterized by a slowly progressing accumulation of
clonal CD5+ B cells. Our laboratory has investigated the role of
transforming growth factor-beta (TGF-beta) and interleukin-4 (IL-4) in the
pathogenesis of B-cell expansion in CLL. In vitro addition of TGF- beta did
not increase spontaneous apoptosis of B cells from most CLL patients, as
determined using the TUNEL method, compared with a twofold increase
observed in cultures of normal B cells. There was similar expression of
TGF-beta type II receptors on both CLL B cells and normal B cells. In
contrast to apoptosis, CLL B-cell proliferation was variably inhibited with
addition of TGF-beta. In vitro addition of IL- 4, previously reported to
promote CLL B-cell survival, dramatically reduced spontaneous apoptosis of
CLL B cells compared with normal B cells. CLL B-cell expression of IL-4
receptors was increased compared to normal B cells. Thus, our results show
aberrant apoptotic responses of CLL B cells to TGF-beta and IL-4, perhaps
contributing to the relative expansion of the neoplastic clone.
Volume 89,
Issue 3,
pp. 941-947,
02/01/1997
Copyright © 1997 by The American Society of Hematology
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