doiSerbia

Prognostic significance of cellular vascular endothelial growth factor (VEGF) expression in the course of chronic myeloid leukaemia

Vidović Ana (Institut za hematologiju, Klinički centar Srbije, Beograd)
Janković Gradimir (Institut za hematologiju, Klinički centar Srbije, Beograd)
Tomin Dragica (Institut za hematologiju, Klinički centar Srbije, Beograd)
Peruničić-Jovanović Maja (Institut za hematologiju, Klinički centar Srbije, Beograd)
Đunić Irena (Institut za hematologiju, Klinički centar Srbije, Beograd)
Đurašinović Vladislava (Institut za hematologiju, Klinički centar Srbije, Beograd)
Čolović Milica (Institut za hematologiju, Klinički centar Srbije, Beograd)

Introduction. Increased angiogenesis in bone marrow is one of the characteristics of chronic myeloid leukaemia (CML), a clonal myeloproliferative disorder that expresses a chimeric bcr/abl protein. Vascular endothelial growth factor (VEGF) is one of the most potent and a specific regulator of angiogenesis which principally targets endothelial cells and regulates several of their functions, including mitogenesis, permeability and migration. The impact of elevated VEGF expression on the course of chronic myeloid leukaemia is unknown. Objective. The aim of this study was the follow-up of VEGF expression during the course of CML. Methods. We studied VEGF expression of 85 CML patients (median age 50 years, range 16-75 years). At the commencement of the study, 29 patients were in chronic phase (CP), 25 in an accelerated phase (AP), and 31 in the blast crisis (BC). The temporal expression (percentage positivity per 1000 analysed cells) VEGF proteins over the course of CML were studied using the immunohistochemical technique utilizing relevant monoclonal antibodies. It was correlated with the laboratory (Hb, WBC and platelet counts, and the percentage of blasts) and clinical parameters (organomegaly, duration of CP, AP, and BC) of disease progression. Results. The expression of VEGF protein was most pronounced in AP (ANOVA, p=0.033). The level of VEGF expression correlated inversely with the degree of splenomegaly (Pearson, r=-0.400, p=0.011). High expression of VEGF correlated with a shorter overall survival (log rank, p=0.042). Conclusion. Immunohistochemically confirmed significance of the expression of VEGF in dependence of the CML stage could be of clinical importance in deciding on the timing therapy. These data suggest that VEGF plays a role in the biology of CML and that VEGF inhibitors should be investigated in CML.

Keywords: chronic myeloid leukaemia, VEGF, prognosis