Blood Levels of Angiogenin and Vascular Endothelial Growth Factor Are Elevated in Myelodysplastic Syndromes and in Acute Myeloid Leukemia

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Abstract
Angiogenesis is of prognostic importance not only in solid tumors but also in malignant blood diseases. We measured levels of vascular endothelial growth factor (VEGF), angiogenin (ANG), and basic fibroblast growth factor (bFGF) in peripheral blood samples from 65 patients with myelodysplastic syndrome (MDS), from 25 patients with de novo acute myeloid leukemia (AML), and from 50 healthy donors. In matched samples, VEGF levels in serum were substantially higher than VEGF levels in plasma (380.7 ± 56 pg/ml vs. 45.3 ± 4.5 pg/ml, mean ± SEM, p < 0.001), whereas serum and plasma levels of ANG were comparable and significantly correlated (r = 0.8; p < 0.01). Compared to normal controls (1.3 ± 0.09 pg), serum levels of VEGF corrected for the peripheral blood platelet count (VEGF/106 platelets, VEGFPLT) were elevated in patients with refractory anemia (RA; 3.1 ± 0.8 pg, p < 0.01), and reached maximal values in patients with advanced stage MDS (RAEB, RAEB-t) (3.5 ± 0.6 pg, p < 0.001), de novo AML (3.6 ± 1.1 pg, p < 0.05), and chronic myelomonocytic leukemia (CMML; 3.7 ± 0.9 pg; p < 0.001). Levels of soluble ANG were elevated in RA (351 ± 25.7 ng/ml, p < 0.001), in RAEB/RAEB-t (402 ± 17.9 ng/ml; p < 0.001), in CMML (413.8 ± 29.5 ng/ml; p < 0.001), and in patients with AML (305.1 ± 17.1 ng/ml; p < 0.01, controls 255.4 ± 8.1 ng/ml). Serum bFGF was neither elevated in MDS nor in AML patients. These results suggest that VEGFPLT is a marker of disease progression in MDS. Moreover, we show for the first time that elevated blood levels of ANG can be found in patients with myeloid malignancies, suggesting a role of ANG in the pathogenesis of these diseases.