Diffuse large B cell lymphoma (DLBCL) is the most common aggressive B cell lymphoma and accounts for nearly 40% of cases of B cell non-Hodgkin lymphoma. DLBCL is generally treated with R-CHOP chemotherapy, but many patients do not respond or relapse after treatment. Here, we analyzed the therapeutic potential of the tumor suppressor microRNA-28 (miR-28) for DLBCL, alone and in combination with the Brutons tyrosine kinase inhibitor ibrutinib. Combination therapy with miR-28 plus ibrutinib potentiated the anti-tumor effects of monotherapy with either agent by inducing a specific transcriptional cell-cycle arrest program that impairs DNA replication. Moreover, we found that downregulation of the miR-28-plus-ibrutinib gene signature correlates with better survival of ABC-DLBCL patients. These results provide evidence for the effectiveness of a new miRNA-based ibrutinib combination therapy for DLBCL and unveil the miR-28-plus-ibrutinib gene signature as a new predictor of outcome in ABC-DLBCL patients.

中文翻译：

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miR-28 加依鲁替尼作为一种新的联合治疗弥漫性大 B 细胞淋巴瘤

弥漫性大 B 细胞淋巴瘤 (DLBCL) 是最常见的侵袭性 B 细胞淋巴瘤，占 B 细胞非霍奇金淋巴瘤病例的近 40%。DLBCL 一般采用 R-CHOP 化疗，但许多患者在治疗后无反应或复发。在这里，我们分析了肿瘤抑制因子 microRNA-28 (miR-28) 单独和与布鲁顿酪氨酸激酶抑制剂依鲁替尼联合治疗 DLBCL 的治疗潜力。与 miR-28 加依鲁替尼的联合治疗通过诱导损害 DNA 复制的特定转录细胞周期停滞程序，增强了任一药物单药治疗的抗肿瘤作用。此外，我们发现 miR-28-plus-ibrutinib 基因标记的下调与 ABC-DLBCL 患者更好的生存率相关。