小儿伯基特淋巴瘤的单细胞转录组学揭示了瘤内异质性和耐药性标志物

IF 12.8 1区 医学 Q1 HEMATOLOGY
Clarissa Corinaldesi, Antony B. Holmes, Gaia Martire, Anna Tosato, Domenico Rizzato, Federica Lovisa, Ilaria Gallingani, Qiong Shen, Lavinia Ferrone, Marian Harris, Kimberly Davies, Luca Molinaro, Umberto Mortara, Angelo Paolo Dei Tos, Kenneth Ofori, Emanuele S. G. D’Amore, Roberto Chiarle, Bo Ngan, Elisa Carraro, Marta Pillon, Shafinaz Hussein, Govind Bhagat, Marco Pizzi, Lara Mussolin, Katia Basso
{"title":"小儿伯基特淋巴瘤的单细胞转录组学揭示了瘤内异质性和耐药性标志物","authors":"Clarissa Corinaldesi, Antony B. Holmes, Gaia Martire, Anna Tosato, Domenico Rizzato, Federica Lovisa, Ilaria Gallingani, Qiong Shen, Lavinia Ferrone, Marian Harris, Kimberly Davies, Luca Molinaro, Umberto Mortara, Angelo Paolo Dei Tos, Kenneth Ofori, Emanuele S. G. D’Amore, Roberto Chiarle, Bo Ngan, Elisa Carraro, Marta Pillon, Shafinaz Hussein, Govind Bhagat, Marco Pizzi, Lara Mussolin, Katia Basso","doi":"10.1038/s41375-024-02431-3","DOIUrl":null,"url":null,"abstract":"<p>Burkitt lymphoma (BL) is the most frequent B-cell lymphoma in pediatric patients. While most patients are cured, a fraction of them are resistant to therapy. To investigate BL heterogeneity and the features distinguishing therapy responders (R) from non-responders (NR), we analyzed by single-cell (sc)-transcriptomics diagnostic EBV-negative BL specimens. Analysis of the non-tumor component revealed a predominance of immune cells and a small representation of fibroblasts, enriched in NR. Tumors displayed patient-specific features, as well as shared subpopulations that expressed transcripts related to cell cycle, signaling pathways and cell-of-origin signatures. Several transcripts were differentially expressed in R versus NR. The top candidate, Tropomyosin 2 (TPM2), a member of the tropomyosin actin filament binding protein family, was confirmed to be significantly higher in NR both at the transcript and protein level. Stratification of patients based on TPM2 expression at diagnosis significantly correlated with prognosis, independently of <i>TP53</i> mutations. These results indicate that BL displays transcriptional heterogeneity and identify candidate biomarkers of therapy resistance.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"12 1","pages":""},"PeriodicalIF":12.8000,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Single-cell transcriptomics of pediatric Burkitt lymphoma reveals intra-tumor heterogeneity and markers of therapy resistance\",\"authors\":\"Clarissa Corinaldesi, Antony B. Holmes, Gaia Martire, Anna Tosato, Domenico Rizzato, Federica Lovisa, Ilaria Gallingani, Qiong Shen, Lavinia Ferrone, Marian Harris, Kimberly Davies, Luca Molinaro, Umberto Mortara, Angelo Paolo Dei Tos, Kenneth Ofori, Emanuele S. G. D’Amore, Roberto Chiarle, Bo Ngan, Elisa Carraro, Marta Pillon, Shafinaz Hussein, Govind Bhagat, Marco Pizzi, Lara Mussolin, Katia Basso\",\"doi\":\"10.1038/s41375-024-02431-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Burkitt lymphoma (BL) is the most frequent B-cell lymphoma in pediatric patients. While most patients are cured, a fraction of them are resistant to therapy. To investigate BL heterogeneity and the features distinguishing therapy responders (R) from non-responders (NR), we analyzed by single-cell (sc)-transcriptomics diagnostic EBV-negative BL specimens. Analysis of the non-tumor component revealed a predominance of immune cells and a small representation of fibroblasts, enriched in NR. Tumors displayed patient-specific features, as well as shared subpopulations that expressed transcripts related to cell cycle, signaling pathways and cell-of-origin signatures. Several transcripts were differentially expressed in R versus NR. The top candidate, Tropomyosin 2 (TPM2), a member of the tropomyosin actin filament binding protein family, was confirmed to be significantly higher in NR both at the transcript and protein level. Stratification of patients based on TPM2 expression at diagnosis significantly correlated with prognosis, independently of <i>TP53</i> mutations. These results indicate that BL displays transcriptional heterogeneity and identify candidate biomarkers of therapy resistance.</p>\",\"PeriodicalId\":18109,\"journal\":{\"name\":\"Leukemia\",\"volume\":\"12 1\",\"pages\":\"\"},\"PeriodicalIF\":12.8000,\"publicationDate\":\"2024-10-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Leukemia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41375-024-02431-3\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Leukemia","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41375-024-02431-3","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

伯基特淋巴瘤(BL)是儿童患者中最常见的 B 细胞淋巴瘤。虽然大多数患者都能治愈,但也有一部分患者对治疗产生耐药性。为了研究布基特淋巴瘤的异质性以及区分治疗应答者(R)和非应答者(NR)的特征,我们通过单细胞(sc)转录组学分析了诊断性EBV阴性布基特淋巴瘤标本。对非肿瘤成分的分析表明,免疫细胞占主导地位,成纤维细胞占少数,在 NR 中富集。肿瘤显示出患者特异性特征,以及表达与细胞周期、信号通路和原发细胞特征相关转录本的共有亚群。有几个转录本在 R 和 NR 中表达不同。最重要的候选转录本--肌球蛋白肌动蛋白丝结合蛋白家族成员之一的肌球蛋白 2 (TPM2)在 NR 中的转录本和蛋白水平均显著升高。根据诊断时 TPM2 的表达对患者进行分层与预后密切相关,与 TP53 突变无关。这些结果表明BL具有转录异质性,并确定了耐药性的候选生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Single-cell transcriptomics of pediatric Burkitt lymphoma reveals intra-tumor heterogeneity and markers of therapy resistance

Single-cell transcriptomics of pediatric Burkitt lymphoma reveals intra-tumor heterogeneity and markers of therapy resistance

Burkitt lymphoma (BL) is the most frequent B-cell lymphoma in pediatric patients. While most patients are cured, a fraction of them are resistant to therapy. To investigate BL heterogeneity and the features distinguishing therapy responders (R) from non-responders (NR), we analyzed by single-cell (sc)-transcriptomics diagnostic EBV-negative BL specimens. Analysis of the non-tumor component revealed a predominance of immune cells and a small representation of fibroblasts, enriched in NR. Tumors displayed patient-specific features, as well as shared subpopulations that expressed transcripts related to cell cycle, signaling pathways and cell-of-origin signatures. Several transcripts were differentially expressed in R versus NR. The top candidate, Tropomyosin 2 (TPM2), a member of the tropomyosin actin filament binding protein family, was confirmed to be significantly higher in NR both at the transcript and protein level. Stratification of patients based on TPM2 expression at diagnosis significantly correlated with prognosis, independently of TP53 mutations. These results indicate that BL displays transcriptional heterogeneity and identify candidate biomarkers of therapy resistance.

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
Leukemia
Leukemia 医学-血液学
CiteScore
18.10
自引率
3.50%
发文量
270
审稿时长
3-6 weeks
期刊介绍: Title: Leukemia Journal Overview: Publishes high-quality, peer-reviewed research Covers all aspects of research and treatment of leukemia and allied diseases Includes studies of normal hemopoiesis due to comparative relevance Topics of Interest: Oncogenes Growth factors Stem cells Leukemia genomics Cell cycle Signal transduction Molecular targets for therapy And more Content Types: Original research articles Reviews Letters Correspondence Comments elaborating on significant advances and covering topical issues
×
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