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慢性淋巴细胞白血病患者循环内皮细胞:临床预后和生物学意义。

Circulating endothelial cells in patients with chronic lymphocytic leukemia: clinical-prognostic and biologic significance.

机构信息

Hematology Section, St. Anna University Hospital, University of Ferrara, Ferrara, Italy.

出版信息

Cancer. 2010 Apr 15;116(8):1926-37. doi: 10.1002/cncr.24961.

DOI:10.1002/cncr.24961
PMID:20166207
Abstract

BACKGROUND

In patients with cancer, circulating endothelial cells (CECs) are increased and are correlated with an aggressive disease course. However, the clinical and biologic significance of CECs in chronic lymphocytic leukemia (CLL) remains uncertain.

METHODS

In 170 patients with CLL, CEC levels were quantified by flow cytometry and were correlated with clinical and biologic data. In addition, CECs were characterized by immunophenotypic, fluorescence in situ hybridization (FISH), and gene expression profile analyses.

RESULTS

In patients with CLL, CECs were increased compared with controls. A higher level of CECs (>20/microL) identified a subset of patients with a more aggressive disease course characterized by a shorter time to first treatment both in univariate and multivariate analyses. In FISH analysis, 7 patients had a significant proportion of CECs and presented with the same cytogenetic lesion of neoplastic lymphocytes and immunophenotypic features of endothelial progenitor cells. The gene expression profile of sorted CECs revealed a molecular pattern, suggesting a derivation from CLL leukemic cells with increased cell survival and proliferation, diminished cell adhesion to extracellular matrix, and enhanced proangiogenic function compared with their normal counterparts.

CONCLUSIONS

The current data suggest that, in CLL, CECs may represent a biologic marker of aggressiveness and disease progression to be considered for new, targeted antiangiogenic treatments.

摘要

背景

在癌症患者中,循环内皮细胞(CECs)增加,并与侵袭性疾病过程相关。然而,CECs 在慢性淋巴细胞白血病(CLL)中的临床和生物学意义仍不确定。

方法

在 170 例 CLL 患者中,通过流式细胞术定量 CEC 水平,并将其与临床和生物学数据相关联。此外,通过免疫表型、荧光原位杂交(FISH)和基因表达谱分析对 CEC 进行特征描述。

结果

与对照组相比,CLL 患者的 CEC 增加。CEC 水平较高(>20/μL)在单变量和多变量分析中均确定了一组疾病进展更为侵袭性的患者,表现为首次治疗的时间更短。在 FISH 分析中,7 例患者 CEC 比例显著,并呈现出与肿瘤性淋巴细胞相同的细胞遗传学病变和内皮祖细胞的免疫表型特征。分选 CEC 的基因表达谱揭示了一种分子模式,表明其来源于 CLL 白血病细胞,具有增加的细胞存活和增殖、减少细胞与细胞外基质的黏附以及增强的促血管生成功能,与正常细胞相比。

结论

目前的数据表明,在 CLL 中,CECs 可能代表一种侵袭性和疾病进展的生物学标志物,可考虑用于新的靶向抗血管生成治疗。

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