Increased serum levels of vascular endothelial growth factor correlate with splenomegaly in polycythemia vera

Abstract 

Angiogenesis has been implicated in the growth, dissemination and metastasis of solid tumours. Several recent studies have shown increased bone marrow vasculature in acute and chronic leukaemia as well as in myelofibrosis and myelodysplastic syndromes. Increased serum and/or cellular levels of vascular endothelial growth factor (VEGF) as the most potent and specific angiogenic factor were reported in acute and chronic leukaemia and multiple myeloma and also predict poor prognosis in these haematological malignancies. Little is known about angiogenesis and VEGF levels in polycythemia. Thus, the serum levels of VEGF (pg/ml) and erythropoietin (U/l) were determined using ultra-sensitive ELISA assays in 16 polycythemia patients (10 with polycythemia vera (PV) and 6 with secondary polycythemia) and correlated with their clinical and laboratory features. The serum levels of VEGF were significantly higher in 90% of PV cases and 60% of secondary polycythemia compared to healthy controls. The median VEGF levels (pg/ml) were 622 (range, 272–4760), 306 (range, 111–408) and 143 (range, 91–282) in PV, secondary polycythemia and healthy controls, respectively. Since serum VEGF reflects both plasma VEGF and platelet released VEGF, the concentration of VEGF per platelet (VEGF/PLT) as pg per 10⁶ platelet was used as a more standardised measure. Splenomegaly emerged as the main factor associated with a marked increase in serum VEGF/PLT levels. On the other hand, the serum erythropoietin levels (U/l) were significantly reduced in PV (range, 1.2–14.3) raised in secondary polycythemia (range, 26–104) compared with normal controls (range, 9.7–31.1), P<0.01.

In conclusion, the present study shows increased VEGF levels in most polycythemia patients, and splenomegaly is associated with a profound increase in VEGF serum levels in these patients. Also, patients with PV have significantly reduced serum levels of erythropoietin compared with secondary polycythemia. Also, serum VEGF/PLT was higher in PV patients treated with phlebotomy alone rather than oral chemotherapy, suggesting a possible advantage for chemotherapy over phlebotomy alone in suppressing the disease progression. Further studies with large number of polycythemia cases are warranted to explore the role of these cytokines in the pathogenesis, diagnosis and/or therapy of polycythemia.

Abbreviations:  Epo, erythropoietin, Hb, haemoglobin, Hct, hematocrit, PV, polycythemia vera, VEGF, vascular endothelial growth factor

Keywords:  Angiogenesis, Erythropoietin, Cytokine, Polycythemia, Splenomegaly, Vascular endothelial growth factor (VEGF)