Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes

Abstract

Angiogenesis has been associated with the growth, dissemination, and metastasis of solid tumors. The aims of this study were to evaluate the vascularity and the levels of angiogenic factors in patients with acute and chronic leukemias and myelodysplastic syndromes (MDS). The numbers of blood vessels were measured in 145 bone marrow biopsies and the levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), tumor necrosis growth factor-α (TNF-α), tumor growth factor-α (TGF-α), and hepatocyte growth factor (HGF) were determined in 417 plasma samples. Except for chronic lymphocytic leukemia (CLL), vascularity was significantly higher in all leukemias and MDS compared with control bone marrows. The highest number of blood vessels and largest vascular area were found in chronic myeloid leukemia (CML). VEGF, bFGF, and HGF plasma levels were significantly increased in acute myeloid leukemia (AML), CML, CLL, chronic myelomonocytic leukemia (CMML), and MDS. HGF, TNF-α, and bFGF but not VEGF were significantly increased in acute lymphoblastic leukemia (ALL). TNF-α levels were significantly increased in all diseases except for AML and MDS. No significant increase was found in TGF-α in any leukemia or MDS. The highest plasma levels of VEGF were in CML, and the highest plasma levels of bFGF were in CLL. The levels of HGF were highest in CMML. These data suggest that vascularity and angiogenic factors are increased in leukemias and MDS and may play a role in the leukemogenic process.

Clinical relevance of vascular endothelial growth factor receptors 1 and 2 in acute myeloid leukaemia and myelodysplastic syndrome

“…A reflection of this may be seen in the inverse, but not significant, correlation between VEGFR-1 and VEGF protein levels, especially in AML (P ¼ 0AE08, R ¼ )0AE24). However, this did not result in major differences in microvessel density in AML and MDS (Aguayo et al, 2000b), probably because of the presence of other angiogenic/anti-angiogenic factors in the bone marrow environment (Majka et al, 2001). Third, cellular levels of VEGFR-2 in bone marrow did not affect patient survival, but significantly correlated with levels of cellular VEGF in both MDS and AML.…”

Significance of angiogenin plasma concentrations in patients with acute myeloid leukaemia and advanced myelodysplastic syndrome

“…The basis for the elevated levels of angiogenin in patients with AML and advanced MDS requires further study. Although bone marrow vascularity in patients with these diseases is significantly higher than in normal individuals, the levels of different angiogenic factors differ, as one would expect (Aguayo et al, 2000). Whether angiogenin is produced by a certain population of malignant cells, bone marrow stroma or both remains to be determined.…”

Effect of inositol hexaphosphate (IP6) on human normal and leukaemic haematopoietic cells

“…It regulates multiple endothelial cell functions, and its biological activities are mediated through at least two receptor tyrosine kinases, Flk-1 and flt-1 (Zachary, 1998). Increased levels of VEGF have been reported in CML as well as in myeloid blasts in human leukaemia and myelodysplastic syndromes, suggesting that VEGF production may play a pathogenetic role in these haematological diseases (Aguayo et al, 2000;Bellamy et al, 2001). These observations may suggest a possible IP 6 anti-angiogenic effect through VEGF downmodulation.…”