Soluble angiogenic factors: Implications for chronic myeloproliferative disorders

Abstract

The role of angiogenesis for the progressive growth and metastatic process of tumours is well established. What is not clear, though, is the clinical prognostic signi®cance of the angiogenic factors in malignant haematological diseases. In this study, we have assessed the plasma and serum levels of two major angiogenic factors, vascular endothelial growth factor (VEGF) and basic ®broblast growth factor (b-FGF) in 55 patients affected by chronic myeloproliferative disorders (CMD). This series included 25 patients with essential thrombocythemia (ET), 10 patients with chronic myelocytic leukaemia (CML), 14 patients with polycythemia vera (PV), and 6 patients with primary myelo®brosis (MF), and they were compared to 20 healthy control subjects. In all patients the plasma VEGF concentration was signi®cantly increased to the healthy control group (P < 0.004). The highest concentrations were found in the patients with ET (178.25 125.22 pg/ml). The VEGF levels were signi®cantly higher in CMD patients with vascular complications than those in CMD patients without complications (P < 0.01). The b-FGF serum levels also appeared to be signi®cantly higher in almost all the CMD patients compared to the control group (P < 0.07). A signi®cant correlation was found between the VEGF levels and the platelet count in the ET patients and the spleen index in the CML patients. VEGF level, in this study, is associated with increased risk of thrombotic complications. There is evidence of increased levels of soluble angiogenic factors in malignant haematological disorders, but their contribution to the progression of diseases is yet unclear. Am.

Anti-inflammatory cytokines hepatocyte growth factor and interleukin-11 are over-expressed in Polycythemia vera and contribute to the growth of clonal erythroblasts independently of JAK2V617F

“…Yet, symptoms of chronic inflammation are observed both in JAK2V617F-mutated MPN and in MPN with no mutation of JAK2, particularly primary myelofibrosis (Geissler et al, 1998;Le Bousse-Kerdile´s and Martyre´, 1999;Wickenhauser et al, 1999;Hermouet et al, 2002;Musolino et al, 2002;Corre-Buscail et al, 2005;Panteli et al, 2005). The findings of the present study of PV patients support the opposite reasoning, that is, that upregulation of certain cytokines linked to inflammation is independent of the acquisition of the JAK2V617F mutation.…”

“…The '46/1' haplotype is also associated with chronic inflammation, notably inflammatory bowel disease (Ferguson et al, 2010). Interestingly, although most evident in primary myelofibrosis, signs of chronic inflammation, such as increased production of inflammatory cytokines, interleukin (IL)-6 and vascular endothelial growth factor, are also observed in PV and in ET (Wickenhauser et al, 1999;Musolino et al, 2002;Panteli et al, 2005;Le Bousse-Kerdile´s and Martyre´, 1999). Inflammation-associated symptoms were long considered consequences of activating mutations of JAK2, but recent clinical trials of JAK2 antagonists showed that drugs not strictly specific for JAK2 were most efficient in reducing inflammation-linked cytokine levels and symptoms, indicating that molecules other than JAK2 were likely involved (Tefferi, 2010).…”

The role of VEGF and a functional link between VEGF and p27Kip1 in acute myeloid leukemia

“…27 VEGF is a critical angiogenic factor that is crucial to disease progression and metastases in solid tumors, 28 and it has been suggested to act as a mediator of disease-associated angiogenesis in patients with myeloid leukemia. 29,30 However, only a few reported studies have shown that VEGF has a prognostic role in predicting patient outcome in leukemia 31 In this study, we have shown that VEGF is highly expressed in 52% of AML patients. VEGF expression is associated with several clinical features.…”

Clinical Correlation of Bone Marrow Microvessel Density in Essential Thrombocythemia

“…Angiogenesis expressed as angiogenic factor’s serum or plasma levels, has been also evaluated in patients with ET [25,26,27,28]. Molica et al [25] found increased serum levels (adjusted for platelet count) in ET patients, but lower than in patients with CML and MMM.…”