Elevated vascular endothelial growth factor (VEGF) serum levels in idiopathic myelofibrosis

Abstract

An increase of angiogenesis has been shown in idiopatic myelofibrosis with myeloid metaplasia (MMM) by microvessel density count method but evaluation of circulating angiogenic factors is still incomplete. In 31 patients affected by MMM and in 12 healthy subjects we evaluated the serum levels of VEGF (vascular endothelial growth factor) and correlated VEGF with clinical and laboratory features of disease. We found that MMM patients had circulating VEGF concentrations much higher than controls (median 1208 ng/ml vs 138 ng/ml, P Ͻ 0.0001). No correlation was found between VEGF and Hb, WBC, PLT, LDH, creatinine, bone marrow cellularity, fibrosis, splenomegaly, hepatomegaly, and therapy. However, in the subgroup of patients with a normal or low VEGF concentration, a direct correlation between VEGF and platelet count (r = 0.90, P = 0.002) was detected. Moreover, patients with a platelet count Ͻ300 × 10 9 /l had VEGF serum levels lower than patients with a higher PLT count (median VEGF 864 vs 1557 pg/ml, P = 0.001). In six patients and in eight controls we also had the opportunity to measure VEGF in the plasma and we calculated that VEGF concentration was much higher in platelet-rich than in platelet-poor plasma and that platetets of MMM patients contained four times more VEGF than those of healthy controls. These results indicate that VEGF is overproduced in MMM, thus confirming an increased angiogenic activity. Platelets are probably a major source of VEGF in MMM but not the only one. Leukemia (2001) 15, 976-980.

Overexpression of FKBP51 in idiopathic myelofibrosis regulates the growth factor independence of megakaryocyte progenitors

“…32 In addition, MKs also synthesize vascular endothelial growth factor and thrombospondin, 2 cytokines that are able to stimulate the bone marrow angiogenesis associated with the myelofibrosis. 33 However, the mechanisms that lead to the release of these cytokines by MKs in the marrow environment are poorly understood. It has been suggested that this was due (1) to dysplastic MKs that die in the marrow, 5 (2) to cell death induced by polymorphonuclear cells after their emperipolesis by MKs, 34,35 or (3) to a spontaneous release of the MK ␣-granule content.…”

Importance of the bone marrow microenvironment in inducing the angiogenic response in multiple myeloma

“…This explains why FGF-2 concentrations in marrow aspirates and peripheral blood correlate with MM activity (Di Raimondo et al, 2000;Sezer et al, 2001;Sato et al, 2002). Bisping et al (2003) have illustrated the expression of highaffinity FGFR-1 through R-4 in RPMI-8226 and U266 MM cell lines and patients' plasma cells, as well as in BMSC, and hence the likelihood of both autocrine and paracrine loops of growth and angiogenesis.…”

Overexpression of vascular endothelial growth factor (VEGF) and its cellular receptor KDR (VEGFR-2) in the bone marrow of patients with acute myeloid leukemia

“…27,29 A recent report has shown that expression of VEGF is restricted to myeloblasts and immature myeloid elements in various MDS subtypes 30 and VEGF has been found to be elevated in patients with idiopathic myelofibrosis. 31 Furthermore, in a series of 99 patients with newly diagnosed AML, Aguayo et al 32 found that increased cellular VEGF is an independent poor prognostic factor in patients with AML. VEGF type C, another member of the vascular endothelial growth factor family, is expressed by leukemic blasts in a significant proportion of patients with AML.…”