文章：

Cereblon结合蛋白表达水平与新诊断的多发性骨髓瘤患者的高倍体性相关

Cereblon-binding proteins expression levels correlate with hyperdiploidy in newly diagnosed multiple myeloma patients

原文发布日期：2019-01-29

DOI: 10.1038/s41408-019-0174-z

类型: Article

开放获取: 是

英文摘要：

Immunomodulatory drugs (IMIDs) are very effective in the treatment of multiple myeloma (MM). The description of their cereblon-mediated mechanism of action was a hallmark in MM research. Although the importance of IMID-induced degradation of cereblon-binding proteins is well described in vitro, the prognostic value of their expression levels in MM cells is less clear. Based on recently published data showing somewhat conflicting RNA levels, we analyzed the association between the levels of the Ikaros family zinc finger protein 1 (IKZF1), IKZF3, and karyopherin subunit alpha 2 (KPNA2) proteins measured by flow cytometry and prognostic parameters in 214 newly diagnosed MM patients who were randomized in the GMMG HD6 trial. No statistically significant associations between the expression levels and age, gender, light chain type, International Staging System (ISS) stage or cytogenetic high- and normal risk groups could be identified. Hyperdiploid MM cells expressed significantly higher levels of IKZF1, IKZF3 and KPNA2 than nonhyperdiploid cells. In contrast, translocation t(11;14) was associated with significantly lower expression levels. In conclusion, the observed overexpression of cereblon-binding proteins in MM cells with gain of chromosomes 5, 9, 11, 15, and 19 is consistent with the previously proposed positive regulation of MYC by IKZF1 and IKZF3, as well as MYC activation in hyperdiploid MM cells.

摘要翻译： 

免疫调节药物（IMiDs）在多发性骨髓瘤（MM）的治疗中非常有效。对其cereblon介导的作用机制的描述是多发性骨髓瘤研究中的一个里程碑。尽管IMiD诱导的cereblon结合蛋白降解的重要性在体外已得到充分描述，但它们在MM细胞中表达水平的预后价值尚不明确。基于最近发表的显示有些矛盾的RNA水平的数据，我们分析了在GMMG HD6试验中随机分组的214名新诊断MM患者中，通过流式细胞术测量的Ikaros家族锌指蛋白1（IKZF1）、IKZF3和karyopherin亚基α2（KPNA2）蛋白水平与预后参数之间的关联。未发现表达水平与年龄、性别、轻链类型、国际分期系统（ISS）分期或细胞遗传学高危和正常风险组之间存在统计学显著关联。超二倍体MM细胞表达的IKZF1、IKZF3和KPNA2水平显著高于非超二倍体细胞。相反，易位t(11;14)与显著较低的表达水平相关。总之，在获得5、9、11、15和19号染色体的MM细胞中观察到的cereblon结合蛋白过表达，与先前提出的IKZF1和IKZF3对MYC的正向调控以及超二倍体MM细胞中MYC的激活一致。

原文链接：

Cereblon-binding proteins expression levels correlate with hyperdiploidy in newly diagnosed multiple myeloma patients