Clinical relevance of Flt1 and Tie1 angiogenesis receptors expression in B-cell chronic lymphocytic leukemia (CLL)
Clinical relevance of Flt1 and Tie1 angiogenesis receptors expression in B-cell chronic lymphocytic leukemia (CLL)
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DOI：
10.1016/s0145-2126(00)00139-9
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发表时间：
2001-04-01
影响因子：
2.7
通讯作者：
Albitar, M
中科院分区：
文献类型：
--
作者：
Aguayo, A;Manshouri, T;Albitar, M
血管生成是一个复杂的过程，受血管内皮细胞生长因子、碱性成纤维细胞生长因子及其受体等多种分子及其受体的密切调控，在实体瘤的生长和转移中起重要作用。血管内皮生长因子和碱性成纤维细胞生长因子在许多实体肿瘤和血液系统肿瘤中的表达和产生已被证实。由于最近发现慢性淋巴细胞性白血病(CLL)患者的白血病细胞中细胞血管内皮生长因子的表达增加，我们决定研究血管生成受体Flt1和Tie1的表达。应用Western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。血清Flt1、Tie1水平与外周血白细胞数(WBC)、淋巴细胞绝对数呈正相关。Flt1水平与细胞内血管内皮生长因子水平相关，而与Tie1水平无关。有趣的是，Tie1与RAI分期密切相关(P=0.04)。Flt1和Tie1与生存期无关，尽管当我们评估早期疾病(RAI 0-II期)的患者时，Tie1水平较高而Flt1水平与较差的生存期无关。这些数据表明，Tie1在B细胞CLL的早期阶段起作用，随着疾病的发展，肿瘤细胞变得独立于Tie1的作用。现在需要进一步的研究来剖析造成这一现象的机制。(C)2001爱思唯尔科学有限公司。保留所有权利。
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. (C) 2001 Elsevier Science Ltd. All rights reserved.