文章：

CD20基因突变引起的不可逆利妥昔单抗耐药淋巴瘤的鉴定

The identification of irreversible rituximab-resistant lymphoma caused by CD20 gene mutations

原文发布日期：2011-04-08

DOI: 10.1038/bcj.2011.11

类型: Original Article

开放获取: 是

英文摘要：

C-terminal mutations of CD20 constitute part of the mechanisms that resist rituximab therapy. Most CD20 having a C-terminal mutation was not recognized by L26 antibody. As the exact epitope of L26 has not been determined, expression and localization of mutated CD20 have not been completely elucidated. In this study, we revealed that the binding site of L26 monoclonal antibody is located in the C-terminal cytoplasmic region of CD20 molecule, which was often lost in mutated CD20 molecules. This indicates that it is difficult to distinguish the mutation of CD20 from under expression of the CD20 protein. To detect comprehensive CD20 molecules including the resistant mutants, we developed a novel monoclonal antibody that recognizes the N-terminal cytoplasm region of CD20 molecule. We screened L26-negative cases with our antibody and found several mutations. A rituximab-binding analysis using the cryopreserved specimen that mutation was identified in CD20 molecules indicated that the C-terminal region of CD20 undertakes a critical role in presentation of the large loop in which the rituximab-binding site locates. Thus, combination of antibodies of two kinds of epitope permits the identification of C-terminal CD20 mutations associated with irreversible resistance to rituximab and may help the decision of the treatment strategy.

摘要翻译： 

CD20的C端突变是导致利妥昔单抗治疗耐药的部分机制。大多数发生C端突变的CD20无法被L26抗体识别。由于L26的确切表位尚未明确，突变CD20的表达与定位尚未完全阐明。本研究发现L26单克隆抗体的结合位点位于CD20分子C端胞质区，而该区域在突变CD20分子中常发生缺失。这表明难以将CD20突变与CD20蛋白低表达进行区分。为全面检测包括耐药突变体在内的CD20分子，我们开发了一种新型单克隆抗体，可识别CD20分子N端胞质区。通过使用该抗体筛查L26阴性病例，我们发现了若干突变。对存在CD20分子突变的冷冻标本进行利妥昔单抗结合分析表明，CD20的C端区域在呈现包含利妥昔单抗结合位点的大环结构中起关键作用。因此，联合使用针对两种表位的抗体可识别与不可逆性利妥昔单抗耐药相关的C端CD20突变，或有助于治疗策略的制定。

原文链接：

The identification of irreversible rituximab-resistant lymphoma caused by CD20 gene mutations