Bairey O, Zimra Y, Shaklai M, Rabizadeh E
Institute of Haematology and the Felsenstein Medical Research Centre, Rabin Medical Centre, Beilinson Campus, Petah Tikva, Israel.
Br J Haematol. 2001 May;113(2):400-6. doi: 10.1046/j.1365-2141.2001.02731.x.
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.
很大比例的B细胞慢性淋巴细胞白血病(B-CLL)细胞表达抗凋亡蛋白Bcl-2。碱性成纤维细胞生长因子(bFGF)已被证明可上调B-CLL细胞系中Bcl-2的表达。血管内皮生长因子(VEGF)已被证明可通过上调Bcl-2的表达来提高内皮细胞的存活率。在本研究中,我们使用商业定量夹心酶免疫测定技术测量了85例CLL患者血清和细胞中的bFGF和VEGF水平。同时使用蛋白质印迹分析检测Bcl-2水平。bFGF的平均血清水平为53.4 pg/ml(范围0-589),VEGF的平均血清水平为459.2 pg/ml(范围33-1793)。bFGF的平均细胞水平为158.3 pg/2×105个细胞(范围0.8-841),VEGF为42.4 pg/2×105个细胞(范围0-244)。血清和细胞bFGF水平之间存在高度相关性(P<0.001),但相应的VEGF水平之间无相关性。在评估Bcl-2水平的69例患者中,有29例(42%)表达了该蛋白。Bcl-2水平与血清bFGF水平呈正相关(P = 0.007)。然而,令人惊讶的是,Bcl-2表达与细胞内VEGF水平呈负相关(P = 0.003)。血清bFGF与疾病随访时间和白细胞计数对数之间也存在正相关。这些发现表明,在CLL中,血管生成相关因子与凋亡相关蛋白表达之间存在相关性,bFGF水平升高可能是Bcl-2水平升高的原因。