Recent studies have demonstrated that the vascular density and the number of VEGF-positive cells are increased in bone marrow of CML patients (Lundberg et al. Am. J. Pathol. 157,15,2000). On this basis we have measured serum concentrations of VEGF and another important soluble mediator of angiogenesis, HGF, in the serum of 30 patients affected by CML. Median age was 55 (range 26-77), median duration of disease 45 months (range 0165). Sixteen patients were receiving treatment with hydroxyurea (HU), 10 with Interferon (IFN) and 4 were not treated at the time of evaluation (two at diagnosis, one in late chronic phase, and 1 in accelerated phase). Serum VEGF and HGF levels were above the upper normal value in 15 and 14 patients respectively. Although in some patients only one of the two factors was elevated, a correlation was present between VEGF and HGF (r=0.48, p= 0.008). In addition, VEGF correlated with PLT (r=0.70, p< 0.0001 ), WBC (r=0.54, p= 0.002) and LDH (r=0.4, p= 0.03). while HGF correlated with WBC (r=0.83, p< 0.0001), LDH (r=0.71, p< 0.0001), splenomegaly (r=0.66, p< 0.0001 ), hepatomegaly (r=0.50, p= 0.005), PLT (r=0.44, p= 0.02), and was inversely correlated with Hb (r= -0.65, p= 0.0001). Fourteen patients at diagnosis or early chronic phase tended to have lower values of both angiogenic factors than patients in late chronic phase or accelerated disease (median VEGF 404 vs 1277; median HGF 935 vs 1835). However, these differences were not statistically significant. On the contrary, a significant difference was found when we divided our patients according to treatment: IFN-treated patients had much lower values of both factors than HU-treated and untreated patients (median value for VEGF 293 vs 1244, p= 0.01 ; median value for HGF 816 vs 2038, p= 0.005 ). Since angiogenic factors, especially VEGF, may be released under normal conditions in response to hypoxia, we also measured erythropoietin (EPO) serum concentration as an index of the hypoxic stimulus. However, neither VEGF, nor HGF, correlated with EPO, indicating that their increased serum concentration were independent from hypoxia. In conclusion, these data indicate that in half of our CML patients, serum levels of angiogenic factors are increased, especially in patients with more advanced disease. Moreover, our data suggest that IFN could exert an anti-angiogenic activity by lowering the levels of some important soluble mediators of angiogenesis.

Low serum levels of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in IFN-treated chronic myeloid leukemia (CML) patients

Di Raimondo, Francesco;Azzaro, Maria Pia;Stagno, Fabio;Palumbo, Giuseppe A.;Giustolisi, Rosario
2000-01-01

Abstract

Recent studies have demonstrated that the vascular density and the number of VEGF-positive cells are increased in bone marrow of CML patients (Lundberg et al. Am. J. Pathol. 157,15,2000). On this basis we have measured serum concentrations of VEGF and another important soluble mediator of angiogenesis, HGF, in the serum of 30 patients affected by CML. Median age was 55 (range 26-77), median duration of disease 45 months (range 0165). Sixteen patients were receiving treatment with hydroxyurea (HU), 10 with Interferon (IFN) and 4 were not treated at the time of evaluation (two at diagnosis, one in late chronic phase, and 1 in accelerated phase). Serum VEGF and HGF levels were above the upper normal value in 15 and 14 patients respectively. Although in some patients only one of the two factors was elevated, a correlation was present between VEGF and HGF (r=0.48, p= 0.008). In addition, VEGF correlated with PLT (r=0.70, p< 0.0001 ), WBC (r=0.54, p= 0.002) and LDH (r=0.4, p= 0.03). while HGF correlated with WBC (r=0.83, p< 0.0001), LDH (r=0.71, p< 0.0001), splenomegaly (r=0.66, p< 0.0001 ), hepatomegaly (r=0.50, p= 0.005), PLT (r=0.44, p= 0.02), and was inversely correlated with Hb (r= -0.65, p= 0.0001). Fourteen patients at diagnosis or early chronic phase tended to have lower values of both angiogenic factors than patients in late chronic phase or accelerated disease (median VEGF 404 vs 1277; median HGF 935 vs 1835). However, these differences were not statistically significant. On the contrary, a significant difference was found when we divided our patients according to treatment: IFN-treated patients had much lower values of both factors than HU-treated and untreated patients (median value for VEGF 293 vs 1244, p= 0.01 ; median value for HGF 816 vs 2038, p= 0.005 ). Since angiogenic factors, especially VEGF, may be released under normal conditions in response to hypoxia, we also measured erythropoietin (EPO) serum concentration as an index of the hypoxic stimulus. However, neither VEGF, nor HGF, correlated with EPO, indicating that their increased serum concentration were independent from hypoxia. In conclusion, these data indicate that in half of our CML patients, serum levels of angiogenic factors are increased, especially in patients with more advanced disease. Moreover, our data suggest that IFN could exert an anti-angiogenic activity by lowering the levels of some important soluble mediators of angiogenesis.
Biochemistry; Immunology; Hematology; Cell Biology
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/358773
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