Exploiting Synthetic Lethality for the Therapy of ABC Diffuse Large B Cell Lymphoma

YangY.; ShafferA.L.; EmreN.C.T.; CeribelliM.; ZhangM.; WrightG.; XiaoW.; PowellJ.; PlatigJ.; KohlhammerH.; YoungR.M.; ZhaoH.; XuW.; BuggyJ.J.; BalasubramanianS.; MathewsL.A.; ShinnP.; GuhaR.; FerrerM.; ThomasC.; WaldmannT.A.; StaudtL.M.

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Exploiting Synthetic Lethality for the Therapy of ABC Diffuse Large B Cell Lymphoma

机译：利用合成杀伤力治疗ABC弥漫性大B细胞淋巴瘤

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Knowledge of oncogenic mutations can inspire therapeutic strategies that are synthetically lethal, affecting cancer cells while sparing normal cells. Lenalidomide is an active agent in the activated B cell-like (ABC) subtype of diffuse large B cell lymphoma (DLBCL), but its mechanism of action is unknown. Lenalidomide kills ABC DLBCL cells by augmenting interferon β (IFNβ) production, owing to the oncogenic MYD88 mutations in these lymphomas. In a cereblon-dependent fashion, lenalidomide downregulates IRF4 and SPIB, transcription factors that together prevent IFNβ production by repressing IRF7 and amplify prosurvival NF-κB signaling by transactivating CARD11. Blockade of B cell receptor signaling using the BTK inhibitor ibrutinib also downregulates IRF4 and consequently synergizes with lenalidomide in killing ABC DLBCLs, suggesting attractive therapeutic strategies.

机译：致癌突变的知识可以激发综合致命性的治疗策略，影响癌细胞，同时保留正常细胞。来那度胺是弥漫性大B细胞淋巴瘤（DLBCL）的活化B细胞样（ABC）亚型中的活性剂，但其作用机理尚不清楚。由于这些淋巴瘤中的致癌性MYD88突变，来那度胺通过增加干扰素β（IFNβ）的产量杀死ABC DLBCL细胞。来那度胺以大脑依赖性的方式下调IRF4和SPIB，这是转录因子，它们通过抑制IRF7共同阻止IFNβ的产生，并通过反式激活CARD11来放大生存性NF-κB信号传导。使用BTK抑制剂依鲁替尼对B细胞受体信号的阻断作用还可以下调IRF4，从而在杀灭ABC DLBCLs中与来那度胺协同作用，提示了诱人的治疗策略。

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《Cancer Cell》 |2012年第6期|共15页
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YangY.; ShafferA.L.; EmreN.C.T.; CeribelliM.; ZhangM.; WrightG.; XiaoW.; PowellJ.; PlatigJ.; KohlhammerH.; YoungR.M.; ZhaoH.; XuW.; BuggyJ.J.; BalasubramanianS.; MathewsL.A.; ShinnP.; GuhaR.; FerrerM.; ThomasC.; WaldmannT.A.; StaudtL.M.;
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正文语种 eng
中图分类肿瘤学;
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1. Exploiting Synthetic Lethality for the Therapy of ABC Diffuse Large B Cell Lymphoma [J] . YangY., ShafferA.L., EmreN.C.T., Cancer Cell . 2012,第6期

机译：利用合成杀伤力治疗ABC弥漫性大B细胞淋巴瘤
2. Autophagy and cell death to target cancer cells: Exploiting synthetic lethality as cancer therapies [J] . ReyjalJ., CormierK., TurcotteS. Advances in Experimental Medicine and Biology . 2014,第Null期

机译：靶向癌细胞的自噬和细胞死亡：利用合成致死性作为癌症疗法
3. A Novel BCL-2 Inhibitor APG-2575 Exerts Synthetic Lethality With BTK or MDM2-p53 Inhibitor in Diffuse Large B-Cell Lymphoma [J] . Luo Qiuyun, Pan Wentao, Zhou Suna, Oncology Research . 2020,第4期

机译：一种新的Bcl-2抑制剂APG-2575用BTK或MDM2-P53抑制剂施加合成致死率，弥漫性大B细胞淋巴瘤
4. Data Mining on Survival Prediction after Chemotherapy for Diffuse Large-B-Cell Lymphoma and Genomics of Metastasis Cancer [C] . Shen LU, Richard SEGALL, Thomas HAHN World multi-conference on systemics, cybernetics and informatics . 2014

机译：弥漫性大B细胞淋巴瘤化疗后生存预测的数据挖掘及转移癌的基因组学研究
5. Effectiveness of Novel Immunotherapy and Chemotherapy Treatments for Follicular and Diffuse Large B-Cell Lymphomas [D] . Butsenko, Dmitriy. 2017

机译：新型免疫疗法和化学疗法对滤泡性和弥漫性大B细胞淋巴瘤的疗效
6. Exploiting Synthetic Lethality for the Therapy of ABC Diffuse Large B Cell Lymphoma [O] . Yibin Yang, Arthur L. Shaffer III, N.C. Tolga Emre, -1

机译：利用合成致死性的aBC弥漫大B细胞淋巴瘤的治疗
7. Exploiting Synthetic Lethality for the Therapy of ABC Diffuse Large B Cell Lymphoma [O] . Yang Yibin, Shaffer Arthur L., Emre N.C. Tolga, 2012

机译：利用合成杀伤力治疗ABC弥漫性大B细胞淋巴瘤

Exploiting Synthetic Lethality for the Therapy of ABC Diffuse Large B Cell Lymphoma

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