A possible role for spontaneous interleukin-8 production by acute myeloid leukemic cells in angiogenesis related processes: Work in progress

Background. Recently, the role of interleukin-8 (IL-8) in angiogenesis was reported. We consequently addressed here the question whether IL-8 produced by acute myeloid leukemia (AML) blasts might have a comparable function. Procedure. In 21 pediatric patients with AML the role of AML derived IL-8 in angiogenesis related processes were investigated. Therefore, IL-8 protein and mRNA expression were measured and endothelial cell (EC) migration and proliferation assays were performed. In addition, bFGF and VEGF mRNA expression were measured by RT-PCR. Results. In the Supernatant of the AML blasts, IL8 protein was present in a varying amount (median 0.86 mug/L, range: 0.1-320 mug/L) and confirmed by RT-PCR. Normal bone marrow mononuclear cells secreted a significant lower amount of IL-8 protein (median: 0.053 mug/L, range: 0.023-0.055 mug/L, P=0.0017). Seven of the 17 tested AML supernatants induced a varying low amount of EC proliferation compared to control media, which was not inhibited by anti-IL-8 antibodies. In contrast, in the EC migration assay, 15 out of the 17 AML supernatants tested, showed an increased EC migration (median fold increase: 1.97, range: 0.66-6.36, P=0.002) compared to control medium. The increase in EC migration could partially be blocked by anti-IL-8 in 59% of the cases (18% decrease, range 0-62%, P = 0.003). Other contributors for the increase in EC migration were also determined. Vascular endothelial growth factor NEGF) transcripts by RT-PCR were demonstrated in six out of the nine tested AML cases, while no transcripts for basic fibroblast growth factor (VEGF) could be shown. Conclusions. Neutralizing anti IL-8 antibodies inhibit EC migration when stimulated with AML supernatant. This suggests a facilitating role for AML-derived IL-8 in an important step in angiogenesis. (C) 2001 Wiley-Liss, Inc.