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Vascular endothelial growth factor, a possible paracrine growth factor in
human acute myeloid leukemia
W Fiedler, U Graeven, S Ergun, S Verago, N Kilic, M Stockschlader and DK Hossfeld
Department of Hematology/Oncology, University Hospital Eppendorf, Hamburg,
Germany.
Vascular endothelial growth factor (VEGF) is a multifunctional cytokine
involved in angiogenesis, inflammation, and wound healing. It is secreted
by a variety of tumor cell lines, including hematopoietic lines. Therefore,
we investigated expression of VEGF and its receptors on fresh leukemic
blasts. VEGF-specific transcripts were detected by polymerase chain
reaction (PCR) in 20 of 28 patients with de novo acute myeloid leukemia
(AML) and in 3 of 5 patients with secondary AML. Using immunocytochemistry,
we found VEGF protein in 2 leukemic cell lines and in 8 AML patients, in
concordance with PCR results. Supernatants of fresh leukemic cells from 24
AML patients contained significantly more VEGF than supernatants from bone
marrow cells of 9 normal donors or of CD34-enriched cells from 3 normal
volunteer donors as determined by an enzyme-linked immunosorbent assay.
VEGF possesses two high-affinity receptors, KDR and FLT1. Using a sensitive
nested PCR assay, we detected expression of FLT1 in 10 of 20 patients with
de novo AML and 3 of 5 patients with secondary AML. KDR was expressed in 4
of 22 patients with de novo AML and 1 of 4 with secondary AML. To study
possible paracrine growth stimulation of AML blasts, endothelial cells from
human umbilical cords were incubated with increasing concentrations of
VEGF. A dose-dependent increase of granulocyte-macrophage colony-
stimulating factor secretion from endothelial cells was identified.
Volume 89,
Issue 6,
pp. 1870-1875,
03/15/1997
Copyright © 1997 by The American Society of Hematology
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