Analyses of the mechanisms of resistance to monoclonal antibody therapy and exploration of overcoming strategies.

我们重点研究了利妥昔单抗化疗后CD20阴性的B细胞淋巴瘤细胞CD20阴性表型改变的现象，并对CD20阴性改变的分子机制进行了分析。研究表明，MS4A1基因表达的异常下调与CD20阴性表型密切相关，这种抑制可能是通过在MS4A1启动子区域募集Sin3-HDAC1蛋白复合体来实现的。CD20阴性表型与利妥昔单抗耐药有关。表观遗传药物可部分刺激下调的CD20表达，导致部分恢复利妥昔单抗的敏感性。

We focused on the phenomenon CD20-negative phenotypic change after performing chemotherapies with rituximab in CD20-positive B-cell lymphoma cells, and the molecular mechanisms of CD20-negative change were analyzed. It appears that aberrant down-regulation of MS4A1 gene expression is closely related to CD20-negative phenotype, and the repression may be introduced by recruitment of Sin3-HDAC1 protein complex to MS4A1 promoter region. CD20-negative phenotype is related to resistance to rituximab therapy. Down-regulated CD20 expression can be partially stimulated by epigenetic drugs resulting in partial restoration of rituximab sensitivity.