Differential expression of chemokine receptors in B cell malignancies
Differential expression of chemokine receptors in B cell malignancies
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DOI：
10.1038/sj.leu.2402107
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发表时间：
2001-05-01
期刊：
影响因子：
11.4
通讯作者：
Dührsen, U
中科院分区：
文献类型：
--
作者：
Dürig, J;Schmücker, U;Dührsen, U
趋化因子是一个由 8-10 kDa 蛋白质组成的家族，具有广泛的生物活性，包括调节白细胞运输、调节造血细胞增殖和粘附细胞外基质分子。我们使用一组趋化因子受体特异性单克隆抗体 (MoAb) 通过多色流式细胞术分析了 B 细胞急性淋巴细胞白血病（前体 B-ALL；六例）、B 细胞慢性淋巴细胞白血病中淋巴细胞相关趋化因子受体 CXCR4、CXCR5、CCR5 和 CCR6 的表达 （B-CLL；31例）、多发性骨髓瘤（10例）、套细胞淋巴瘤（MCL，4例）、滤泡性淋巴瘤（FL，3例）和毛细胞白血病（HCL，5例）。我们证明，CXCR4、CXCR5 和 CCR6 在这些 B 淋巴细胞增殖性疾病中存在差异表达，具体取决于所研究的恶性 B 细胞群的成熟阶段。特别是，我们发现 CXCR4 在未成熟的 ALL 母细胞上强烈表达，而没有观察到 CXCR5、CCR5 和 CCR6 的表面免疫反应性。相比之下，对应于更成熟的外周B细胞亚群（即B-CLL和MCL）的非霍奇金淋巴瘤（NHL）表现出CXCR4和CXCR5的高表达水平，对终末分化骨髓瘤细胞的分析显示CXCR4、CXCR5和CCR6的下调，而在正常B细胞中不表达的CCR5在大多数非霍奇金淋巴瘤细胞中也不表达。 NHL，然而，在 5 例 HCL 病例中的 3 例中观察到 CCR5 染色，这是恶性造血细胞中跨谱系异常趋化因子受体表达的第一个例子。
Chemokines are a family of 8-10 kDa proteins with a wide range of biological activities including the regulation of leukocyte trafficking, modulation of haemopoietic cell proliferation and adhesion to extracellular matrix molecules. Using a panel of chemokine receptor-specific monoclonal antibodies (MoAb) in a multicolour flow cytometry approach we analysed the expression of the lymphocyte-associated chemokine receptors CXCR4 CXCR5, CCR5 and CCR6 in B cell acute lymphoblastic leukaemia (precursor B-ALL; six cases), B cell chronic lymphocytic leukaemia (B-CLL; 31 cases), multiple myeloma (10 cases), mantle cell lymphoma (MCL, four cases), follicular lymphoma (FL, three cases) and hairy cell leukaemia (HCL, five cases). We demonstrate that CXCR4, CXCR5 and CCR6 are differentially expressed in these B lymphoproliferative disorders depending on the maturational stage of the malignant B cell population investigated. In particular, we found that CXCR4 is strongly expressed on immature ALL blasts whereas no surface immunoreactivity for CXCR5, CCR5 and CCR6 was observed. By contrast, non-Hodgkin's lymphomas (NHLs) corresponding to more mature peripheral B cell subsets (ie B-CLL and MCL) exhibited high expression levels of CXCR4 and CXCR5, Analysis of terminally differentiated myeloma cells revealed a down-regulation of CXCR4, CXCR5 and CCR6, CCR5, which is not expressed in normal B cells, was also absent from the majority of NHLs, However, CCR5 staining was seen in three of five cases of HCL, representing the first example of cross-lineage aberrant chemokine receptor expression in malignant haemopoietic cells.