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Chronic Lymphocytic Leukemic B Cells But Not Normal B Cells Are
Rescued From Apoptosis by Contact With Normal Bone Marrow Stromal Cells
L. Lagneaux,
A. Delforge,
D. Bron,
C. De Bruyn, and
P. Stryckmans
From the Service de Médecine Interne et Laboratoire
d'Investigation Clinique Henri Tagnon, Institut J. Bordet, Brussels,
Belgium.
The leukemic B lymphocytes from chronic lymphocytic leukemic (CLL)
patients have a long survival in vivo, although ex vivo they rapidly
die by apoptosis. To further investigate the mechanism of this, we have
studied the influence of bone marrow stromal cells from normal subjects
on apoptosis of B-CLL cells and normal umbilical cord blood (UCB) B
lymphocytes. After 48 hours of incubation in medium alone, leukemic and
normal B cells showed, respectively, 22 ± 3% and 31 ± 5% of apoptosis. Cocultures with stromal cells reduced the
percentage of leukemic cells undergoing apoptosis (8 ± 2%, P < .0005) and prevented the loss of bcl-2 protein expression. In
contrast, stromal cells slightly increased normal B-cell apoptosis (37 ± 6%). Direct contact between leukemic cells and stromal cells was
found to be essential for inhibition of leukemic cell apoptosis; indeed, separation of leukemic cells from stromal cells by microporous membrane increased spontaneous apoptosis, and comparable results were
obtained with stromal cell conditioned medium. The difference in
behavior observed between normal and leukemic B cells plated on stromal
cells can be explained by the fact that only a few normal B cells
adhere to stromal cells in comparison with B-CLL cells. B-CLL cell
adhesion to stromal cells is mediated by  1 and 2
integrins acting simultaneously. Contact between B-CLL cells and bone
marrow stromal cells seems to play a major role in the accumulation and
survival of B-CLL cells in the bone marrow.
Blood, Vol. 91 No. 7 (April 1), 1998:
pp. 2387-2396
© 1998 by The American Society of Hematology.
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