• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

生命早期感染会耗尽小鼠模型中超二倍体 B 细胞急性淋巴细胞白血病中的白血病前细胞。

Early-life infection depletes preleukemic cells in a mouse model of hyperdiploid B-cell acute lymphoblastic leukemia.

机构信息

Michael Cuccione Childhood Cancer Research Program, BC Children's Hospital Research Institute, Vancouver, BC, Canada.

Division of Infectious Diseases, Department of Pediatrics, The University of British Columbia, Vancouver, BC, Canada.

出版信息

Blood. 2024 Aug 22;144(8):809-821. doi: 10.1182/blood.2024025038.

DOI:10.1182/blood.2024025038
PMID:38875504
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11375503/
Abstract

Epidemiological studies report opposing influences of infection on childhood B-cell acute lymphoblastic leukemia (B-ALL). Although infections in the first year of life appear to exert the largest impact on leukemia risk, the effect of early pathogen exposure on the fetal preleukemia cells (PLC) that lead to B-ALL has yet to be reported. Using cytomegalovirus (CMV) infection as a model early-life infection, we show that virus exposure within 1 week of birth induces profound depletion of transplanted E2A-PBX1 and hyperdiploid B-ALL cells in wild-type recipients and in situ-generated PLC in Eμ-ret mice. The age-dependent depletion of PLC results from an elevated STAT4-mediated cytokine response in neonates, with high levels of interleukin (IL)-12p40-driven interferon (IFN)-γ production inducing PLC death. Similar PLC depletion can be achieved in adult mice by impairing viral clearance. These findings provide mechanistic support for potential inhibitory effects of early-life infection on B-ALL progression and could inform novel therapeutic or preventive strategies.

摘要

流行病学研究报告称，感染对儿童急性 B 淋巴细胞白血病（B-ALL）有相反的影响。尽管生命第一年的感染似乎对白血病风险的影响最大，但早期病原体暴露对导致 B-ALL 的胎儿白血病前体细胞（PLC）的影响尚未报道。我们使用巨细胞病毒（CMV）感染作为模型的早期生命感染，表明出生后 1 周内的病毒暴露会导致野生型受体中移植的 E2A-PBX1 和高倍体 B-ALL 细胞以及 Eμ-ret 小鼠原位产生的 PLC 明显耗竭。PLC 的年龄依赖性耗竭源于新生儿中 STAT4 介导的细胞因子反应升高，高水平的白细胞介素（IL）-12p40 驱动的干扰素（IFN）-γ产生诱导 PLC 死亡。通过损害病毒清除，在成年小鼠中也可以实现类似的 PLC 耗竭。这些发现为早期生命感染对 B-ALL 进展的潜在抑制作用提供了机制支持，并可能为新的治疗或预防策略提供信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/11375503/75d07c3c30ee/BLOOD_BLD-2024-025038-gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/11375503/b336db42a190/BLOOD_BLD-2024-025038-ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/11375503/289b2078aedc/BLOOD_BLD-2024-025038-gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/11375503/b152dbe1edac/BLOOD_BLD-2024-025038-gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/11375503/24eed61a7584/BLOOD_BLD-2024-025038-gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/11375503/85bea38aceaa/BLOOD_BLD-2024-025038-gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/11375503/b1ab854c3ccf/BLOOD_BLD-2024-025038-gr5ac.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/11375503/fbfe042a1efc/BLOOD_BLD-2024-025038-gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/11375503/75d07c3c30ee/BLOOD_BLD-2024-025038-gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/11375503/b336db42a190/BLOOD_BLD-2024-025038-ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/11375503/289b2078aedc/BLOOD_BLD-2024-025038-gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/11375503/b152dbe1edac/BLOOD_BLD-2024-025038-gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/11375503/24eed61a7584/BLOOD_BLD-2024-025038-gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/11375503/85bea38aceaa/BLOOD_BLD-2024-025038-gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/11375503/b1ab854c3ccf/BLOOD_BLD-2024-025038-gr5ac.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/11375503/fbfe042a1efc/BLOOD_BLD-2024-025038-gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f0a/11375503/75d07c3c30ee/BLOOD_BLD-2024-025038-gr7.jpg

相似文献

1
Early-life infection depletes preleukemic cells in a mouse model of hyperdiploid B-cell acute lymphoblastic leukemia.生命早期感染会耗尽小鼠模型中超二倍体 B 细胞急性淋巴细胞白血病中的白血病前细胞。
Blood. 2024 Aug 22;144(8):809-821. doi: 10.1182/blood.2024025038.
2
The Eμ-Ret mouse is a novel model of hyperdiploid B-cell acute lymphoblastic leukemia.Eμ-Ret 小鼠是一种新型的高倍体 B 细胞急性淋巴细胞白血病模型。
Leukemia. 2024 May;38(5):969-980. doi: 10.1038/s41375-024-02221-x. Epub 2024 Mar 22.
3
Initiating and cancer-propagating cells in TEL-AML1-associated childhood leukemia.TEL-AML1相关儿童白血病中的起始细胞和癌症增殖细胞
Science. 2008 Jan 18;319(5861):336-9. doi: 10.1126/science.1150648.
4
Discordance of MLL-rearranged (MLL-R) infant acute lymphoblastic leukemia in monozygotic twins with spontaneous clearance of preleukemic clone in unaffected twin.单卵双胞胎中MLL重排（MLL-R）婴儿急性淋巴细胞白血病的不一致性，未受影响的双胞胎中白血病前克隆自发清除。
Blood. 2009 Jun 25;113(26):6691-4. doi: 10.1182/blood-2009-01-202259. Epub 2009 May 1.
5
IFN-γ directly inhibits murine B-cell precursor leukemia-initiating cell proliferation early in life.IFN-γ 可早期直接抑制小鼠 B 细胞前体细胞白血病起始细胞的增殖。
Eur J Immunol. 2017 May;47(5):892-899. doi: 10.1002/eji.201646806. Epub 2017 Apr 11.
6
fusion pediatric B acute lymphoblastic leukemia in disguise behind the eyes - an unusual clinicopathologic presentation with hyperdiploid clone.伪装于眼部背后的融合型小儿B淋巴细胞急性白血病——一种伴有超二倍体克隆的不寻常临床病理表现
Leuk Lymphoma. 2024 Jun;65(6):852-856. doi: 10.1080/10428194.2024.2320827. Epub 2024 Feb 26.
7
Loss of Pax5 Exploits Sca1-BCR-ABL Susceptibility to Confer the Metabolic Shift Essential for pB-ALL.Pax5 缺失利用 Sca1-BCR-ABL 易感性导致代谢重编程，这对 pB-ALL 是必需的。
Cancer Res. 2018 May 15;78(10):2669-2679. doi: 10.1158/0008-5472.CAN-17-3262. Epub 2018 Feb 28.
8
The evolution of B precursor leukemia in the Emu-ret mouse.鸸鹋视网膜小鼠中B前体白血病的演变
Blood. 1998 Jul 1;92(1):273-82.
9
Monoclonal antibodies specific to the acute lymphoblastic leukemia t(1;19)-associated E2A/pbx1 chimeric protein: characterization and diagnostic utility.针对急性淋巴细胞白血病t(1;19)相关E2A/pbx1嵌合蛋白的单克隆抗体：特性与诊断应用
Blood. 1997 Apr 15;89(8):2909-14.
10
Identification of preleukemic precursors of hyperdiploid acute lymphoblastic leukemia in cord blood.脐血中高倍体急性淋巴细胞白血病的白血病前期前体细胞的鉴定
Genes Chromosomes Cancer. 2004 May;40(1):38-43. doi: 10.1002/gcc.20010.

引用本文的文献

1
Early Infection Incidence and Risk of Acute Leukemia Development Among Mexican Children.墨西哥儿童早期感染发病率及急性白血病发病风险
Cancers (Basel). 2025 Feb 21;17(5):733. doi: 10.3390/cancers17050733.

本文引用的文献

1
The Eμ-Ret mouse is a novel model of hyperdiploid B-cell acute lymphoblastic leukemia.Eμ-Ret 小鼠是一种新型的高倍体 B 细胞急性淋巴细胞白血病模型。
Leukemia. 2024 May;38(5):969-980. doi: 10.1038/s41375-024-02221-x. Epub 2024 Mar 22.
2
Age and ligand specificity influence the outcome of pathogen engagement on preleukemic and leukemic B-cell precursor populations.年龄和配体特异性影响病原体与前白血病和白血病 B 细胞前体群相互作用的结果。
Blood Adv. 2023 Nov 28;7(22):7087-7099. doi: 10.1182/bloodadvances.2023010782.
3
Immune stress suppresses innate immune signaling in preleukemic precursor B-cells to provoke leukemia in predisposed mice.
免疫应激抑制前白血病前体 B 细胞中的先天免疫信号传导，从而在易患小鼠中引发白血病。
Nat Commun. 2023 Aug 24;14(1):5159. doi: 10.1038/s41467-023-40961-z.
4
Cytomegalovirus proteins, maternal pregnancy cytokines, and their impact on neonatal immune cytokine profiles and acute lymphoblastic leukemogenesis in children.巨细胞病毒蛋白、母体孕期细胞因子及其对儿童新生儿免疫细胞因子谱和急性淋巴细胞白血病发生的影响。
Haematologica. 2022 Sep 1;107(9):2266-2270. doi: 10.3324/haematol.2022.280826.
5
In Utero Development and Immunosurveillance of B Cell Acute Lymphoblastic Leukemia.在体发育和 B 细胞急性淋巴细胞白血病的免疫监视
Curr Treat Options Oncol. 2022 Apr;23(4):543-561. doi: 10.1007/s11864-022-00963-3. Epub 2022 Mar 16.
6
NK and CD8+ T cell phenotypes predict onset and control of CMV viremia after kidney transplant.NK 和 CD8+ T 细胞表型可预测肾移植后 CMV 病毒血症的发生和控制。
JCI Insight. 2021 Nov 8;6(21):e153175. doi: 10.1172/jci.insight.153175.
7
Genetic Alterations in Childhood Acute Lymphoblastic Leukemia: Interactions with Clinical Features and Treatment Response.儿童急性淋巴细胞白血病的基因改变：与临床特征及治疗反应的相互作用
Cancers (Basel). 2021 Aug 12;13(16):4068. doi: 10.3390/cancers13164068.
8
An intact gut microbiome protects genetically predisposed mice against leukemia.完整的肠道微生物群可保护遗传易患白血病的小鼠免受白血病侵害。
Blood. 2020 Oct 29;136(18):2003-2017. doi: 10.1182/blood.2019004381.
9
History of Early Childhood Infections and Acute Lymphoblastic Leukemia Risk Among Children in a US Integrated Health-Care System.美国综合医疗体系中儿童早期感染史与急性淋巴细胞白血病风险的关系。
Am J Epidemiol. 2020 Oct 1;189(10):1076-1085. doi: 10.1093/aje/kwaa062.
10
Advantages and Limitations of the Neonatal Immune System.新生儿免疫系统的优势与局限
Front Pediatr. 2020 Jan 28;8:5. doi: 10.3389/fped.2020.00005. eCollection 2020.