CXCR4 expression enhances diffuse large B cell lymphoma dissemination and decreases patient survival. J Pathol. 2015,235(3):445-455.

The chemokine receptor CXCR4 has been implicated in the migration and trafficking of malignant B cells in several haematological malignancies. Over-expression of CXCR4 has been identified in haematological tumours, but data concerning the role of this receptor in diffuse large B cell lymphoma (DLBCL) are lacking. CXCR4 is a marker of poor prognosis in various neoplasms, correlating with metastatic disease and decreased survival of patients. We studied CXCR4 involvement in cell migration in vitro and dissemination in vivo. We also evaluated the prognostic significance of CXCR4 in 94 biopsies of DLBCL patients. We observed that the level of expression of CXCR4 in DLBCL cell lines correlated positively with in vitro migration. Expression of the receptor was also associated with increased engraftment and dissemination, and decreased survival time in NOD/SCID mice. Furthermore, administration of a specific CXCR4 antagonist, AMD3100, decreased dissemination of DLBCL cells in a xenograft mouse model. In addition, we found that CXCR4 expression is an independent prognostic factor for shorter overall survival and progression-free survival in DLBCL patients. These results show that CXCR4 mediates dissemination of DLBCL cells and define for the first time its value as an independent prognostic marker in DLBCL patients.

在一些血液系统恶性肿瘤中，趋化因子受体CXCR4牵涉了恶性B细胞的迁移和播散。目前某些血液系统肿瘤中已经鉴定了CXCR4的过度表达，然而该受体在弥漫大B细胞淋巴瘤（DLBCL）中所扮演的角色仍然未知。多种肿瘤中CXCR4是一个预后不良的标记，与转移性疾病关联，并降低患者的生存。作者研究了CXCR4在体外细胞迁移和体内播散过程的作用，并且在94例经活组织检查的DLBCL患者中评估了CXCR4的预后意义。作者观察到在DLBCL细胞系中CXCR4的表达水平与体外细胞迁移密切相关，同时CXCR4的表达能够增强移植瘤并且减少NOD/SCID鼠的生存时间，而且一种特异性CXCR4拮抗剂AMD3100，能够减少DLBCL细胞在小鼠模型移植瘤中的播散。此外，作者发现CXCR4的表达是DLBCL患者总生存期和无进展生存率短的一个独立预后因素。以上结果表明CXCR4调节DLBCL细胞的播散，并且是DLBCL患者的一个独立预后标记。