3D-Q-FISH/端粒/TRF2纳米技术发现端粒/鞘磷脂/维生素AC复合物逐渐紊乱是典型霍奇金淋巴瘤的共同致病分子/空间分母。

IF 5.1 2区 生物学 Q2 CELL BIOLOGY
Cells Pub Date : 2024-10-23 DOI:10.3390/cells13211748
Hans Knecht, Tina Petrogiannis-Haliotis, Sherif Louis, Sabine Mai
{"title":"3D-Q-FISH/端粒/TRF2纳米技术发现端粒/鞘磷脂/维生素AC复合物逐渐紊乱是典型霍奇金淋巴瘤的共同致病分子/空间分母。","authors":"Hans Knecht, Tina Petrogiannis-Haliotis, Sherif Louis, Sabine Mai","doi":"10.3390/cells13211748","DOIUrl":null,"url":null,"abstract":"<p><p>The bi- or multinucleated Reed-Sternberg cell (RS) is the diagnostic cornerstone of Epstein-Barr Virus (EBV)-positive and EBV-negative classical Hodgkin lymphoma (cHL). cHL is a germinal center (GC)-derived B-cell disease. Hodgkin cells (H) are the mononuclear precursors of RS. An experimental model has to fulfill three conditions to qualify as common pathogenic denominator: (i) to be of GC-derived B-cell origin, (ii) to be EBV-negative to avoid EBV latency III expression and (iii) to support permanent EBV-encoded oncogenic latent membrane protein (LMP1) expression upon induction. These conditions are unified in the EBV-, diffuse large B-Cell lymphoma (DLBCL) cell line BJAB-tTA-LMP1. 3D reconstructive nanotechnology revealed spatial, quantitative and qualitative disturbance of telomere/shelterin interactions in mononuclear H-like cells, with further progression during transition to RS-like cells, including progressive complexity of the karyotype with every mitotic cycle, due to BBF (breakage/bridge/fusion) events. The findings of this model were confirmed in diagnostic patient samples and correlate with clinical outcomes. Moreover, in vitro, significant disturbance of the lamin AC/telomere interaction progressively occurred. In summary, our research over the past three decades identified cHL as the first lymphoid malignancy driven by a disturbed telomere/shelterin/lamin AC interaction, generating the diagnostic RS. Our findings may act as trailblazer for tailored therapies in refractory cHL.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"13 21","pages":""},"PeriodicalIF":5.1000,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545283/pdf/","citationCount":"0","resultStr":"{\"title\":\"3D-Q-FISH/Telomere/TRF2 Nanotechnology Identifies a Progressively Disturbed Telomere/Shelterin/Lamin AC Complex as the Common Pathogenic, Molecular/Spatial Denominator of Classical Hodgkin Lymphoma.\",\"authors\":\"Hans Knecht, Tina Petrogiannis-Haliotis, Sherif Louis, Sabine Mai\",\"doi\":\"10.3390/cells13211748\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The bi- or multinucleated Reed-Sternberg cell (RS) is the diagnostic cornerstone of Epstein-Barr Virus (EBV)-positive and EBV-negative classical Hodgkin lymphoma (cHL). cHL is a germinal center (GC)-derived B-cell disease. Hodgkin cells (H) are the mononuclear precursors of RS. An experimental model has to fulfill three conditions to qualify as common pathogenic denominator: (i) to be of GC-derived B-cell origin, (ii) to be EBV-negative to avoid EBV latency III expression and (iii) to support permanent EBV-encoded oncogenic latent membrane protein (LMP1) expression upon induction. These conditions are unified in the EBV-, diffuse large B-Cell lymphoma (DLBCL) cell line BJAB-tTA-LMP1. 3D reconstructive nanotechnology revealed spatial, quantitative and qualitative disturbance of telomere/shelterin interactions in mononuclear H-like cells, with further progression during transition to RS-like cells, including progressive complexity of the karyotype with every mitotic cycle, due to BBF (breakage/bridge/fusion) events. The findings of this model were confirmed in diagnostic patient samples and correlate with clinical outcomes. Moreover, in vitro, significant disturbance of the lamin AC/telomere interaction progressively occurred. In summary, our research over the past three decades identified cHL as the first lymphoid malignancy driven by a disturbed telomere/shelterin/lamin AC interaction, generating the diagnostic RS. Our findings may act as trailblazer for tailored therapies in refractory cHL.</p>\",\"PeriodicalId\":9743,\"journal\":{\"name\":\"Cells\",\"volume\":\"13 21\",\"pages\":\"\"},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2024-10-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545283/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cells\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://doi.org/10.3390/cells13211748\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cells","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.3390/cells13211748","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

双核或多核里德-斯滕伯格细胞(RS)是 Epstein-Barr Virus(EBV)阳性和 EBV 阴性典型霍奇金淋巴瘤(cHL)的诊断基石。霍奇金细胞(H)是RS的单核前体。实验模型必须满足三个条件才能成为共同致病分母:(i) 源自生殖中心的 B 细胞;(ii) EBV 阴性,以避免 EBV 潜伏 III 的表达;(iii) 在诱导时支持 EBV 编码的致癌潜伏膜蛋白 (LMP1) 的永久表达。这些条件在EBV-弥漫大B细胞淋巴瘤(DLBCL)细胞系BJAB-tTA-LMP1中得到了统一。三维重建纳米技术揭示了单核 H 型细胞中端粒/端粒蛋白相互作用的空间、定量和定性紊乱,并在向 RS 型细胞过渡的过程中进一步发展,包括由于 BBF(断裂/桥接/融合)事件导致核型在每个有丝分裂周期中逐渐复杂化。该模型的研究结果在诊断患者样本中得到证实,并与临床结果相关。此外,在体外,片层蛋白 AC 与细胞膜的相互作用也逐渐发生了明显的紊乱。总之,我们在过去三十年的研究中发现,cHL是第一种由端粒/helterin/板层蛋白AC相互作用紊乱驱动的淋巴恶性肿瘤,从而产生了诊断性RS。我们的研究结果可作为难治性 cHL 定制疗法的开路先锋。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
3D-Q-FISH/Telomere/TRF2 Nanotechnology Identifies a Progressively Disturbed Telomere/Shelterin/Lamin AC Complex as the Common Pathogenic, Molecular/Spatial Denominator of Classical Hodgkin Lymphoma.

The bi- or multinucleated Reed-Sternberg cell (RS) is the diagnostic cornerstone of Epstein-Barr Virus (EBV)-positive and EBV-negative classical Hodgkin lymphoma (cHL). cHL is a germinal center (GC)-derived B-cell disease. Hodgkin cells (H) are the mononuclear precursors of RS. An experimental model has to fulfill three conditions to qualify as common pathogenic denominator: (i) to be of GC-derived B-cell origin, (ii) to be EBV-negative to avoid EBV latency III expression and (iii) to support permanent EBV-encoded oncogenic latent membrane protein (LMP1) expression upon induction. These conditions are unified in the EBV-, diffuse large B-Cell lymphoma (DLBCL) cell line BJAB-tTA-LMP1. 3D reconstructive nanotechnology revealed spatial, quantitative and qualitative disturbance of telomere/shelterin interactions in mononuclear H-like cells, with further progression during transition to RS-like cells, including progressive complexity of the karyotype with every mitotic cycle, due to BBF (breakage/bridge/fusion) events. The findings of this model were confirmed in diagnostic patient samples and correlate with clinical outcomes. Moreover, in vitro, significant disturbance of the lamin AC/telomere interaction progressively occurred. In summary, our research over the past three decades identified cHL as the first lymphoid malignancy driven by a disturbed telomere/shelterin/lamin AC interaction, generating the diagnostic RS. Our findings may act as trailblazer for tailored therapies in refractory cHL.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Cells
Cells Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
9.90
自引率
5.00%
发文量
3472
审稿时长
16 days
期刊介绍: Cells (ISSN 2073-4409) is an international, peer-reviewed open access journal which provides an advanced forum for studies related to cell biology, molecular biology and biophysics. It publishes reviews, research articles, communications and technical notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. Full experimental and/or methodical details must be provided.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信