Prognostic significance of hepatocyte growth factor and microvessel bone marrow density in patients with chronic myeloid leukaemia

Abstract

Objective. The aims of the study were: (1) to perform a complex angiogenic assessment in chronic myeloid leukaemia (CML) patients using multiple parameters: bone marrow microvessel density (MVD), bone marrow immunohistochemical cellular expressions of vascular endothelial growth factor (VEGF) and its receptor KDR, as well as hepatocyte growth factor (HGF) and its receptor MET, and the plasma VEGF and HGF; and (2) to determine the clinical significance of these factors for patients with CML. Material and methods. The VEGF and HGF plasma levels were analysed by ELISA in 38 newly diagnosed CML patients. Immunohistochemical methods were used to visualize the MVD as well as the cellular VEGF/KDR and HGF/MET expression. Results. We found an increased MVD, cellular VEGF/KDR and HGF/MET expression and elevated plasma VEGF and HGF in CML patients. The plasma HGF, cellular HGF and MET expression correlated with the CML phase. The plasma HGF correlated with all markers reflecting the tumour burden (leucocytes, blast percentage, splenomegaly and LDH) as well as with the phase of CML and overall survival of the patients. Cox regression analysis determined the prognostic relevance of HGF and MVD parameters, but not for the plasma VEGF and cellular VEGF and KDR. Conclusions. Using a complex angiogenic assessment we determined an increased angiogenesis in CML patients. No prognostic relevance was found for VEGF plasma levels or VEGF/KDR cellular bone marrow expression. The increased cellular HGF and MET expressions could be considered high‐risk factors for these patients. Plasma HGF and MVD were shown to be independent prognostic parameters for patients' survival.

• Angiogenesis
• chronic myeloid leukaemia
• HGF
• VEGF

Acknowledgements

This research was supported by grants from the Varna University of Medicine, Bulgaria, and the National Science Fund of Bulgaria. The technical assistance of Associate Professor Vesselin Hadzhiev and Valentina Petkova is gratefully acknowledged.