12th Congress of the European Hematology ... - Haematologica

12 th Congress of the European Hematology Association
tion are very complex. Further studies on IAPs/IAP antagonists system
in CLL to elucidate these mechanisms and to assess its potential prognostic
usefulness seem to be warranted.
0521
THE EFFECT OF THE B-CLL MICROENVIRONMENT ON CD38 EXPRESSION BY THE
MALIGNANT CLONE
P.E.M. Patten, 1 A.S.G. Buggins, 1 J. Richards, 1 A. Wotherspoon, 2
J. Salisbury, 1 T. Hamblin, 1 G.J. Mufti, 1 S. Devereux1 1 2 King's College London, LONDON; Royal Marsden Hospital, LONDON,
United Kingdom
In order to determine whether microenvironment derived signals
might influence CD38 expression in B-cell chronic lymphocytic
leukemia (B-CLL), we compared levels of this molecule in peripheral
blood (PB), bone marrow (BM), splenic red pulp (RP) and splenic white
pulp (WP). In 35 paired BM and PB samples, significantly higher CD38
expression was observed on BM B-CLL cells compared to PB (27% vs
19%, p=0.009). Five splenic samples infiltrated with B-CLL were examined
by confocal immunofluorescence microscopy. In three cases with
detectable CD38 expression, a significantly higher percentage of CD38
was found expressed by tumor cells in the WP, an area containing Ki67 +
tumor cells and T-cells, compared to RP. We therefore hypothesized that
non-malignant cell derived signals within the leukemic microenvironment
might be responsible for the level of CD38 expression in B-CLL.
To test this theory, we examined the effect of co-culture of B-CLL cells
with T lymphocytes using an in-vitro system aimed at mimicking the
tumor microenvironment. B-CLL cells were cultured at a 4:1 ratio with
CD3/CD28 bead activated autologous T-cells. CD38 expression by B-
CLL cells increased significantly in 15/15 cases over the 6-day culture
period, an effect most marked with cell to cell contact. Proliferation of
tumor cells was also induced and was more marked in cases with higher
initial levels of CD38. A parallel reduction in apoptosis was also
observed. Immunofluorescence microscopy of B-CLL lymph node
showed that Ki67 + tumor cells were significantly more likely to be in
close contact with activated CD4 + T-cells than Ki67 – cells (p