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CLL 的循环微环境:类滋养细胞与肿瘤相关巨噬细胞有关吗?

Circulating microenvironment of CLL: are nurse-like cells related to tumor-associated macrophages?

机构信息

Department of Cancer Genetics, Medical University of Lublin, Radziwillowska 11, 20-080 Lublin, Poland.

出版信息

Blood Cells Mol Dis. 2013 Apr;50(4):263-70. doi: 10.1016/j.bcmd.2012.12.003. Epub 2013 Jan 11.

DOI:10.1016/j.bcmd.2012.12.003
PMID:23313631
Abstract

B-cell chronic lymphocytic leukemia (B-CLL) is one of the most common hematologic malignancies in Western countries. Accumulation of leukemic lymphocytes in peripheral blood, bone marrow and secondary lymphatic organs of CLL patients is due to decreased apoptosis rather than to increased proliferation. The former is driven by signals from a specific microenvironment, created by stromal cells of mesenchymal origin, follicular dendritic cells, T lymphocytes and others. Nurse-like cells (NLCs) were first described to differentiate from peripheral blood mononuclear cells of CLL patients in vitro, then they have been also found in proliferation centers of their lymphatic tissues. Like tumor-associated macrophages (TAMs) in solid tumors, nurse-like cells promote survival of CLL lymphocytes. NLC gene expression patterns suggest their similarity to TAMs and differ between patients depending on ZAP70 protein expression status. NLC number in vitro corresponds with CD14 expressing cell count and beta-2-microglobulin serum level, and positively correlates with leukemic lymphocyte viability. As NLCs strongly express genes for adhesion molecules and secrete chemokines of antiapoptotic activity, they should be considered as a target for anti-microenvironment therapy of this incurable disease.

摘要

B 细胞慢性淋巴细胞白血病(B-CLL)是西方国家最常见的血液恶性肿瘤之一。CLL 患者外周血、骨髓和次级淋巴器官中白血病淋巴细胞的积累是由于凋亡减少而不是增殖增加所致。前者是由特定微环境的信号驱动的,这些信号由间充质来源的基质细胞、滤泡树突状细胞、T 淋巴细胞等产生。首先描述了类滋养细胞(NLCs)从 CLL 患者的外周血单个核细胞在体外分化,然后在其淋巴组织的增殖中心也发现了它们。像实体瘤中的肿瘤相关巨噬细胞(TAMs)一样,类滋养细胞促进 CLL 淋巴细胞的存活。NLC 的基因表达模式表明它们与 TAMs 相似,并且根据 ZAP70 蛋白表达状态在患者之间存在差异。体外 NLC 数量与表达 CD14 的细胞计数和β-2-微球蛋白血清水平相对应,并与白血病淋巴细胞活力呈正相关。由于 NLCs 强烈表达黏附分子基因并分泌具有抗凋亡活性的趋化因子,因此应将其视为治疗这种不可治愈疾病的抗微环境治疗的靶点。

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