Bcl-2 expression correlates positively with serum basic fibroblast growth factor (bFGF) and negatively with cellular vascular endothelial growth factor (VEGF) in patients with chronic lymphocytic leukaemia.
A large proportion of B-chronic lymphocytic leukaemia (B-CLL) cells express the anti-apoptotic protein Bcl-2. Basic fibroblast growth factor (bFGF) has been shown to upregulate the expression of Bcl-2 in B-CLL cell lines. Vascular endothelial growth factor (VEGF) has been shown to enhance the survival of endothelial cells by upregulating the expression of Bcl-2. In the present study, we measured serum and cellular levels of bFGF and VEGF in 85 patients with CLL using a commercial quantitative sandwich enzyme immunoassay technique. Levels of Bcl-2 were also assayed concomitantly using Western blot analysis. The mean serum level of bFGF was 53.4 pg/ml (range 0-589) and that of VEGF 459.2 pg/ml (range 33-1793). The mean cellular level of bFGF was 158.3 pg/2 x 105 cells (range 0.8-841) and VEGF, 42.4 pg/2 x 105 cells (range 0-244). A high correlation was found between serum and cellular bFGF levels (P < 0.001), but not between the corresponding VEGF levels. Twenty-nine of 69 patients (42%) evaluated for Bcl-2 level, expressed it. The Bcl-2 level was positively correlated with the serum bFGF level (P = 0.007). However, surprisingly there was a negative correlation between Bcl-2 expression and intracellular VEGF level (P = 0.003). A positive correlation was also found between serum bFGF and disease follow-up time and log white blood cell count. These findings indicate that in CLL there is a correlation between angiogenesis-related factors and apoptosis-related protein expression, and elevated bFGF levels may account for the elevated Bcl-2 levels.
Bairey
O
O
Institute of Haematology and the Felsenstein Medical Research Centre, Rabin Medical Centre, Beilinson Campus, Petah Tikva, Israel. obairey@post.tau.ac.il
Zimra
Y
Y
Shaklai
M
M
Rabizadeh
E
E
D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016009:Chi-Square Distribution; D004591:Electrophoresis, Polyacrylamide Gel; D016228:Endothelial Growth Factors / Q000032:analysis / Q000097:blood* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000097:blood*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000276:immunology / Q000473:pathology; D007958:Leukocyte Count; D008214:Lymphocytes / Q000737:chemistry; D008222:Lymphokines / Q000032:analysis / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000911:Antibodies, Monoclonal; D016228:Endothelial Growth Factors; D008222:Lymphokines; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2