Transcriptional Regulation and Biochemistry Unit, Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20852, USA.
Blood. 2012 Nov 1;120(18):3756-63. doi: 10.1182/blood-2012-01-405951. Epub 2012 Sep 11.
We have analyzed the role of the REL family members in Hodgkin lymphoma (HL). shRNA targeting of each REL member showed that HL was uniquely dependent on relB, in contrast to several other B-cell lymphomas. In addition, relA and c-rel shRNA expression also decreased HL cell viability. In exploring relB activation further, we found stable NF-κB inducing kinase (NIK) protein in several HL cell lines and that NIK shRNA also affected HL cell line viability. More importantly, 49 of 50 HL patient biopsies showed stable NIK protein, indicating that NIK and the noncanonical pathway are very prevalent in HL. Lastly, we have used a NIK inhibitor that reduced HL but not other B-cell lymphoma cell viability. These data show that HL is uniquely dependent on relB and that the noncanonical pathway can be a therapeutic target for HL. Furthermore, these results show that multiple REL family members participate in the maintenance of a HL phenotype.
我们分析了 REL 家族成员在霍奇金淋巴瘤（HL）中的作用。针对每个 REL 成员的 shRNA 表明，HL 独特地依赖于 relB，而不是其他几种 B 细胞淋巴瘤。此外，relA 和 c-rel shRNA 的表达也降低了 HL 细胞的活力。在进一步探索 relB 的激活时，我们发现几种 HL 细胞系中存在稳定的 NF-κB 诱导激酶（NIK）蛋白，并且 NIK shRNA 也影响 HL 细胞系的活力。更重要的是，50 例 HL 患者活检中有 49 例显示稳定的 NIK 蛋白，表明 NIK 和非经典途径在 HL 中非常普遍。最后，我们使用了一种 NIK 抑制剂，它降低了 HL 但不降低其他 B 细胞淋巴瘤细胞的活力。这些数据表明，HL 独特地依赖于 relB，并且非经典途径可以成为 HL 的治疗靶点。此外，这些结果表明，多个 REL 家族成员参与维持 HL 表型。
