Role of CD21 antigen in diffuse large B-cell lymphoma and its clinical significance
Role of CD21 antigen in diffuse large B-cell lymphoma and its clinical significance
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DOI：
10.1111/j.1365-2141.2004.05226.x
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发表时间：
2004-11-01
影响因子：
6.5
通讯作者：
Fujita, S
中科院分区：
文献类型：
--
作者：
Otsuka, M;Yakushijin, Y;Fujita, S
免疫学和分子技术的最新进展促使人们提出改变肿瘤分类和治疗策略的建议。细胞表面抗原现在很容易获得，肿瘤起源和临床特征现在很容易识别。然而，在弥漫性大B细胞淋巴瘤（DLBCL），血液系统恶性肿瘤的异质性形式之一，肿瘤表面抗原的临床意义还没有得到很好的记录。我们分析了50例新诊断的DLBCL患者肿瘤的肿瘤表面抗原，根据其临床特征，并随访患者平均3.7年。统计学分析显示，CD 21表达与DLBCL患者的死亡率呈显著负相关（CD 21阴性vs阳性;相对危险度= 2.36，P < 0.05）。作为这些临床观察的结果，我们在基因转染后产生了CD 21过表达（CD 21（+））淋巴瘤细胞系，并分析了免疫功能低下小鼠体内肿瘤细胞的生长。仅用载体转染子和作为对照的亲本细胞攻击的小鼠在50天内死亡。相比之下，注射CD 21（+）转染子的小鼠肿瘤生长显著减少，83%的小鼠长期存活（与对照组相比; P < 0.05）。有趣的是，所有建立的CD 21（+）转染子（来自不同批量的6个克隆）在体外细胞培养期间显示同型聚集，并且抗CD 21抗体不阻断这种聚集。CD 21的表达与DLBCL体内存活率的增加密切相关。CD 21的表达可能与其他细胞粘附分子的表达间接相关。
Recent advances in immunological and molecular technology have prompted proposals to change tumour classification and treatment strategies. Cell surface antigens are now easy to access, and tumour origins and clinical characteristics are now readily identifiable. However, in diffuse large B-cell lymphoma (DLBCL), one of the heterogeneous forms of haematological malignancy, the clinical significance of tumour surface antigens has not been well documented. We analysed the tumour surface antigens of 50 tumours from newly diagnosed DLBCL patients by flow cytometry in accordance with their clinical characteristics and followed the patients for a median 3.7 years. Statistical analysis showed that CD21 expression was significantly negatively associated with mortality in DLBCL (CD21 negative versus positive; relative risk = 2.36, P < 0.05). As a result of these clinical observations, we generated CD21-overexpressed (CD21(+)) lymphoma cell lines after gene transfection and analysed tumour cell growth in vivo in immunocompromised mice. Mice challenged with vector-only transfectants and parental cells as controls died within 50 d. In contrast, mice injected with CD21(+) transfectants exhibited significantly reduced tumour growth and 83% survived long term (versus control groups; P < 0.05). Interestingly, all established CD21(+) transfectants (six clones from different bulks) showed homotypic aggregation during in vitro cell culture, and anti-CD21 antibodies did not block this aggregation. Expression of CD21 is strongly associated with increased survival in DLBCL in vivo. CD21 expression may be indirectly concerned with the expression of additional cell adhesion molecules.