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


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.
Zhelyazkova
A G
AG
Department of Clinical Haematology, University Hospital St. Marina Varna, Varna University of Medicine, Varna, Bulgaria. azhelyazkova@gmail.com
Tonchev
A B
AB
Kolova
P
P
Ivanova
L
L
Gercheva
L
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000098:blood supply / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002452:Cell Count; D017228:Hepatocyte Growth Factor / Q000097:blood*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000473:pathology*; D055806:Microvessels / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met; D017978:Receptors, Growth Factor / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D040301:Vascular Endothelial Growth Factor Receptor-2