具有 JAK2/PD-L2 扩增的弥漫大 B 细胞淋巴瘤表现出类似于 PMBCL 的 CNA 模式，临床结局较差，类似于 MYD88 L265P 突变的患者。
DLBCL with amplification of JAK2/PD-L2 exhibits PMBCL-like CNA pattern and worse clinical outcome resembling those with MYD88 L265P mutation.
机构信息
Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, China.
出版信息
BMC Cancer. 2020 Aug 27;20(1):816. doi: 10.1186/s12885-020-07293-3.
BACKGROUND
Recently, copy number alteration (CNA) of 9p24.1 were demonstrated in 10% of diffuse large b-cell lymphoma (DLBCL), with gene expression and mutation profiles that were similar to those of primary mediastinal large B-cell lymphoma (PMBCL). However, their CNA-based profile and clinical impact still remain unclear.
METHODS
Multiplex ligation-dependent probe amplification were employed to investigate the prevalence of JAK2/PD-L2 amplification in DLBCL and their CNA-based pattern of driver genes. The clinical outcome and characteristics were also analyzed.
RESULTS
Using unsupervised hierarchical clustering, a small group of DLBCL (10.5%, 8/76) was clustered together with PMBCL as Cluster_2, demonstrating amplification of JAK2 (100%,8/8) and PD-L2 (75.0%,6/8). This subgroups of DLBCL demonstrated significant higher expression of PD-L1 than those with MYD88 L265P mutation(p = 0.024). And they exhibited dismal OS and PFS as compared with DLBCL_others(p = 0.003 and 0.001, respectively), which is similar to DLBCL with MYD88 L265P mutation.
CONCLUSIONS
DLBCL with amplification of JAK2/PD-L2 exhibits CNA pattern that is similar to PMBCL, and demonstrates unfavorable clinical outcome that resembles those with MYD88 L265P mutation. It is essential to identify this subgroup of DLBCL who may acquire more benefits from the JAK2 and PD-L1 signaling inhibition.
背景
最近，9p24.1 的拷贝数改变（CNA）在 10%的弥漫性大 B 细胞淋巴瘤（DLBCL）中被证实，其基因表达和突变谱与原发性纵隔大 B 细胞淋巴瘤（PMBCL）相似。然而，它们基于 CNA 的特征和临床影响仍不清楚。
方法
采用多重连接依赖性探针扩增技术检测 JAK2/PD-L2 扩增在 DLBCL 中的发生率及其驱动基因的 CNA 模式。还分析了临床结局和特征。
结果
通过无监督层次聚类，一小部分 DLBCL（10.5%，8/76）与 PMBCL 一起聚类为 Cluster_2，表现出 JAK2（100%，8/8）和 PD-L2（75.0%，6/8）的扩增。该亚组的 DLBCL 表现出比 MYD88 L265P 突变的 DLBCL 更高的 PD-L1 表达（p=0.024）。与 DLBCL_others 相比，它们的 OS 和 PFS 明显更差（分别为 p=0.003 和 0.001），与 MYD88 L265P 突变的 DLBCL 相似。
结论
扩增 JAK2/PD-L2 的 DLBCL 表现出与 PMBCL 相似的 CNA 模式，其临床结局与 MYD88 L265P 突变的 DLBCL 相似。识别出这种亚组的 DLBCL，他们可能从 JAK2 和 PD-L1 信号抑制中获得更多益处。
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