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Elevated intracellular level of basic fibroblast growth factor correlates
with stage of chronic lymphocytic leukemia and is associated with
resistance to fludarabine
T Menzel, Z Rahman, E Calleja, K White, EL Wilson, R Wieder and J Gabrilove
Molecular Therapeutics Program, Sloan-Kettering Institute, New York, NY
10021, USA.
Chronic lymphocytic leukemia (CLL) is characterized by delayed senescence
and slow accumulation of monoclonal, small lymphocytes. Basic fibroblast
growth factor (bFGF) is a pleiotropic cytokine that plays a role in
hematopoiesis and apoptosis. Elevated bFGF levels have been detected in
urine from patients with a variety of neoplastic diseases including various
leukemias; however, the cellular source of the bFGF has not been
determined. In this study, the intracellular bFGF level in lymphocytes of
36 patients with B-CLL and 15 normal donors was determined using an
enzyme-linked immunoassay. In cells derived from patients with high-risk
disease, the median level of intracellular bFGF was 381.5 pg/2 x 10(5)
cells, compared with a median of 90.5 pg/2 x 10(5) cells in patients with
intermediate disease. In patients with low- risk disease, the median bFGF
level was 4.9 pg/2 x 10(5) cells, and in normal controls, it was 6.0 pg/2 x
10(5) cells. The difference in the bFGF levels was significant for the
comparison between low- and intermediate-risk (P = .00119), low- and
high-risk (P < .0001), and intermediate- and high-risk disease (P =
.0001). Immunofluorescent stains of peripheral blood mononuclear cells
confirmed CLL lymphocytes as a cellular source of bFGF. To evaluate the
potential contribution of elevated intracellular bFGF levels to the
phenotype of CLL cells, leukemic cells were cultured in vitro with an
apoptotic stimulus (fludarabine). CLL cells with high intracellular levels
of bFGF appeared to be more resistant to fludarabine treatment. The
addition of bFGF to fludarabine-treated CLL cells resulted in a delay of
apoptosis and prolonged survival. These data suggest that bFGF may
contribute to the resistance of CLL cells to an apoptotic stimulus.
Volume 87,
Issue 3,
pp. 1056-1063,
02/01/1996
Copyright © 1996 by The American Society of Hematology
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