Aguayo A, Manshouri T, O'Brien S, Keating M, Beran M, Koller C, Kantarjian H, Rogers A, Albitar M
Department of Leukemia, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 72, Houston, TX , 77030-4095, USA.
Leuk Res. 2001 Apr;25(4):279-85. doi: 10.1016/s0145-2126(00)00139-9.
Angiogenesis, a complex process tightly controlled by several molecules including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) along with their receptors, plays a major role in the growth and metastasis of solid tumors. The expression and production of VEGF and bFGF have been documented in numerous solid tumors and hematopoietic neoplasms. Having recently shown increased expression of cellular VEGF in the leukemic cells of patients with chronic lymphocytic leukemia (CLL) we decided to investigate the expression of angiogenic receptors Flt1 and Tie1. Levels of Tie1 and Flt1 proteins were measured in leukemic cells from 231 patients with B-cell CLL using Western blot analysis and solid-phase radioimmunoassay (RIA). A strong correlation was found between Flt1 and Tie1 levels and white blood cell count (WBC) and absolute lymphocyte counts. Levels of Flt1 but not Tie1 correlated with levels of cellular VEGF. Interestingly, Tie1 correlated well with Rai stage (P=0.04). Flt1 and Tie1 did not correlate with survival, although when we evaluated the patients with early disease (Rai stage 0-II), higher levels of Tie1 but not of Flt1 correlated with worse survival. These data suggest that Tie1 plays a role in the early stages of B-cell CLL and as the disease progresses, the tumor cells become independent from the effects of Tie1. Further studies are now needed to dissect the mechanisms responsible for this phenomenon.
血管生成是一个由多种分子严格控制的复杂过程，这些分子包括血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（bFGF）及其受体，在实体瘤的生长和转移中起主要作用。VEGF和bFGF的表达及产生已在众多实体瘤和造血系统肿瘤中得到证实。最近我们发现慢性淋巴细胞白血病（CLL）患者白血病细胞中细胞VEGF表达增加，因此决定研究血管生成受体Flt1和Tie1的表达。采用蛋白质印迹分析和固相放射免疫分析（RIA）检测了231例B细胞CLL患者白血病细胞中Tie1和Flt1蛋白的水平。发现Flt1和Tie1水平与白细胞计数（WBC）和绝对淋巴细胞计数之间存在强相关性。Flt1水平与细胞VEGF水平相关，而Tie1水平与细胞VEGF水平无关。有趣的是，Tie1与Rai分期相关性良好（P=0.04）。Flt1和Tie1与生存率无关，不过当我们评估早期疾病（Rai分期0-II）患者时，较高的Tie1水平而非Flt1水平与较差的生存率相关。这些数据表明，Tie1在B细胞CLL的早期阶段起作用，随着疾病进展，肿瘤细胞变得不受Tie1影响。现在需要进一步研究来剖析导致这种现象的机制。
