Tomita Akihiro
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine.
J Clin Exp Hematop. 2016;56(2):89-99. doi: 10.3960/jslrt.56.89.
CD20 is a differentiation related cell surface phosphoprotein that is expressed during early pre-B cell stages until plasma cell differentiation, and is a suitable molecular target for B-cell malignancies by monoclonal antibodies such as rituximab, ofatumumab, obinutuzumab and others. CD20 expression is confirmed in most B-cell malignancies; however, the protein expression level varies in each patient, even in de novo tumors, and down-modulation of CD20 expression after chemoimmunotherapy with rituximab, resulting in rituximab resistance, has been recognized in the clinical setting. Recent reports suggest that genetic and epigenetic mechanisms are correlated with aberrantly low CD20 expression in de novo tumors and relapsed/refractory disease after using rituximab. Furthermore, some targeting drugs, such as lenalidomide, bortezomib and ibrutinib, directly or indirectly affect CD20 protein expression. CD20-negative phenotypically-changed DLBCL after rituximab use tends to show an aggressive clinical course and poor outcome with resistance to not only rituximab, but also conventional salvage chemo-regimens. Understanding of the mechanisms of CD20-negative phenotype may contribute to establish strategies for overcoming chemo-refractory B-cell malignancies. In this manuscript, recent progress of research on molecular and clinical features of CD20 protein and CD20-negative B-cell malignancies was reviewed.
CD20是一种与分化相关的细胞表面磷蛋白，在早期前B细胞阶段直至浆细胞分化阶段均有表达，是利妥昔单抗、奥法妥木单抗、奥滨尤妥珠单抗等单克隆抗体治疗B细胞恶性肿瘤的合适分子靶点。大多数B细胞恶性肿瘤中均证实有CD20表达；然而，即使在原发肿瘤中，每位患者的蛋白表达水平也存在差异，并且在利妥昔单抗化疗免疫治疗后CD20表达下调导致利妥昔单抗耐药，这在临床中已得到认可。最近的报告表明，遗传和表观遗传机制与原发肿瘤以及使用利妥昔单抗后的复发/难治性疾病中CD20异常低表达相关。此外，一些靶向药物，如来那度胺、硼替佐米和伊布替尼，直接或间接影响CD20蛋白表达。使用利妥昔单抗后出现CD20阴性表型改变的弥漫性大B细胞淋巴瘤（DLBCL）往往表现出侵袭性临床病程和不良预后，不仅对利妥昔单抗耐药，对传统挽救化疗方案也耐药。了解CD20阴性表型的机制可能有助于制定克服化疗难治性B细胞恶性肿瘤的策略。在本手稿中，综述了关于CD20蛋白和CD20阴性B细胞恶性肿瘤分子及临床特征的研究最新进展。
