不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel：ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
基因组分析确定了结外自然杀伤/T 细胞淋巴瘤的不同遗传亚型
英文原题：Genomic profiling identifies distinct genetic subtypes in extra-nodal natural killer/T-cell lymphoma.
查看英文原题
Genomic profiling identifies distinct genetic subtypes in extra-nodal natural killer/T-cell lymphoma.
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中文摘要
结外NK/T细胞淋巴瘤，鼻型（ENKTCL）是一种高度侵袭性的EB病毒相关淋巴瘤，通常表现为鼻腔和鼻旁区域受累。我们收集了一个大型ENKTCL系列（n = 209），进行了全面的基因组分析和相关临床研究。国际淋巴瘤预后指数（IPI）、疾病部位、分期、淋巴结肿大和肝肿大与总生存期相关。遗传分析揭示了JAK/STAT3通路的频繁致癌激活以及肿瘤抑制基因（TSGs）和与表观基因组调控相关基因的改变。整合基因组分析，包括复发突变和基因组拷贝数改变，使用共识聚类识别出七个不同的遗传簇，这些簇与不同的临床结果相关，从而构成了以前未识别的风险组。来自亚洲和西班牙裔族群的ENTKCL的遗传谱显示出惊人的相似性，表明共享的发病机制和肿瘤进化。有趣的是，我们发现激活STAT3突变与TSG PRDM1缺失在促进NK细胞生长和存活方面的新功能合作。
本研究为进一步分析提供了遗传路线图，并促进了对这种侵袭性淋巴瘤可操作治疗机会的研究。
展开英文摘要原文
Extra-nodal NK/T-cell lymphoma, nasal type (ENKTCL) is a highly aggressive Epstein-Barr virus associated lymphoma, typically presenting in the nasal and paranasal areas.
We assembled a large series of ENKTCL (n = 209) for comprehensive genomic analysis and correlative clinical study. The International Lymphoma Prognostic Index (IPI), site of disease, stage, lymphadenopathy, and hepatomegaly were associated with overall survival. Genetic analysis revealed frequent oncogenic activation of the JAK/STAT3 pathway and alterations in tumor suppressor genes (TSGs) and genes associated with epigenomic regulation.
Integrated genomic analysis including recurrent mutations and genomic copy number alterations using consensus clustering identified seven distinct genetic clusters that were associated with different clinical outcomes, thus constituting previously unrecognized risk groups.
The genetic profiles of ENTKCLs from Asian and Hispanic ethnic groups showed striking similarity, indicating shared pathogenetic mechanism and tumor evolution. Interestingly, we discovered a novel functional cooperation between activating STAT3 mutations and loss of the TSG, PRDM1, in promoting NK-cell growth and survival.
This study provides a genetic roadmap for further analysis and facilitates investigation of actionable therapeutic opportunities in this aggressive lymphoma.
论文信息
- 作者
- Dong G、Liu X、Wang L、Yin W、Bouska A、Gong Q、Shetty K、Chen L
- 第一作者单位
- Department of Pathology, City of Hope National Medical Center, Duarte, CA, 91010, USA.United States
- 通讯作者单位
- Department of Pathology, City of Hope National Medical Center, Duarte, CA, 91010, USA. jochan@coh.org.United States
- 文献类型
- 美国 NIH 资助研究 · 非美国政府资助研究
- 期刊
- Leukemia2022 Aug
- 原文标识
- PubMed 35697790 · DOI 10.1038/s41375-022-01623-z
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