• 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

EWSR1/ELF5通过抑制p53/p21通路诱导急性髓系白血病。

EWSR1/ELF5 induces acute myeloid leukemia by inhibiting p53/p21 pathway.

作者信息

Endo Akifumi, Tomizawa Daisuke, Aoki Yuki, Morio Tomohiro, Mizutani Shuki, Takagi Masatoshi

机构信息

Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan.

Division of Leukemia and Lymphoma, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.

出版信息

Cancer Sci. 2016 Dec;107(12):1745-1754. doi: 10.1111/cas.13080. Epub 2016 Nov 25.

DOI:10.1111/cas.13080
PMID:27627705
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5198945/
Abstract

The Ewing sarcoma breakpoint region 1 (EWSR1) gene is known to fuse with various partner genes to promote the development of the Ewing sarcoma family of tumors and other sarcomas. In contrast, the association of EWSR1 chimeric fusion genes with leukemia has rarely been reported. We identified a novel EWSR1-associated chimeric fusion gene in a patient with acute myeloid leukemia harboring 46, XY, t (11; 22) (p13; q12) karyotype abnormality. The patient was refractory to intensified chemotherapy including hematopoietic stem cell transplantation. Total RNA paired-end sequencing identified a novel chimeric fusion gene as EWSR1/ELF5, a member of the E26 transformation-specific transcription factor family. Transduction of EWSR1/ELF5 to NIH3T3 cells induced transformation by attenuating with the p53/p21-dependent pathway. The injection of EWSR1/ELF5-transduced NIH3T3 cells into NSG-SCID mice systematically induced the development of tumors in vivo. These results revealed the oncogenic potency of EWSR1/ELF5.

摘要

已知尤因肉瘤断点区域1（EWSR1）基因会与多种伙伴基因融合，从而促进尤因肉瘤家族肿瘤及其他肉瘤的发展。相比之下，EWSR1嵌合融合基因与白血病的关联鲜有报道。我们在一名急性髓系白血病患者中发现了一种新的EWSR1相关嵌合融合基因，该患者核型异常为46，XY，t（11；22）（p13；q12）。该患者对包括造血干细胞移植在内的强化化疗无效。全RNA配对末端测序确定了一种新的嵌合融合基因为EWSR1/ELF5，它是E26转化特异性转录因子家族的一员。将EWSR1/ELF5转导至NIH3T3细胞可通过p53/p21依赖途径减弱而诱导细胞转化。将转导了EWSR1/ELF5的NIH3T3细胞注射到NSG-SCID小鼠体内可系统性地诱导肿瘤在体内发生。这些结果揭示了EWSR1/ELF5的致癌潜能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/5198945/4014a4c00c36/CAS-107-1745-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/5198945/6c02def39b22/CAS-107-1745-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/5198945/55aaaf40c900/CAS-107-1745-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/5198945/04a050a0852d/CAS-107-1745-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/5198945/3ccab2e95bd2/CAS-107-1745-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/5198945/0950a68e4b84/CAS-107-1745-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/5198945/832e8e5ca8d2/CAS-107-1745-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/5198945/4014a4c00c36/CAS-107-1745-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/5198945/6c02def39b22/CAS-107-1745-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/5198945/55aaaf40c900/CAS-107-1745-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/5198945/04a050a0852d/CAS-107-1745-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/5198945/3ccab2e95bd2/CAS-107-1745-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/5198945/0950a68e4b84/CAS-107-1745-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/5198945/832e8e5ca8d2/CAS-107-1745-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a345/5198945/4014a4c00c36/CAS-107-1745-g007.jpg

相似文献

1
EWSR1/ELF5 induces acute myeloid leukemia by inhibiting p53/p21 pathway.EWSR1/ELF5通过抑制p53/p21通路诱导急性髓系白血病。
Cancer Sci. 2016 Dec;107(12):1745-1754. doi: 10.1111/cas.13080. Epub 2016 Nov 25.
2
A novel t(4;22)(q31;q12) produces an EWSR1-SMARCA5 fusion in extraskeletal Ewing sarcoma/primitive neuroectodermal tumor.一个新型的 t(4;22)(q31;q12) 导致了骨外尤文肉瘤/原始神经外胚层肿瘤中 EWSR1-SMARCA5 融合。
Mod Pathol. 2011 Mar;24(3):333-42. doi: 10.1038/modpathol.2010.201. Epub 2010 Nov 26.
3
Novel TNS3-MAP3K3 and ZFPM2-ELF5 fusion genes identified by RNA sequencing in multicystic mesothelioma with t(7;17)(p12;q23) and t(8;11)(q23;p13).通过RNA测序在伴有t(7;17)(p12;q23)和t(8;11)(q23;p13)的多囊性间皮瘤中鉴定出的新型TNS3-MAP3K3和ZFPM2-ELF5融合基因。
Cancer Lett. 2015 Feb 28;357(2):502-9. doi: 10.1016/j.canlet.2014.12.002. Epub 2014 Dec 4.
4
Mixed Phenotype Acute Leukemia, B/Myeloid (Bilineal and Biphenotypic), With t(2;22)(q35;q12);EWSR1-FEV.混合表型急性白血病，B/髓系（双系和双表型），伴t(2;22)(q35;q12);EWSR1-FEV
J Pediatr Hematol Oncol. 2021 Apr 1;43(3):e388-e394. doi: 10.1097/MPH.0000000000001934.
5
A novel EWSR1-CREB3L1 fusion transcript in a case of small cell osteosarcoma.一个小细胞骨肉瘤中新型的 EWSR1-CREB3L1 融合转录本。
Genes Chromosomes Cancer. 2011 Dec;50(12):1054-62. doi: 10.1002/gcc.20923. Epub 2011 Aug 24.
6
Detection and characterization of EWSR1/ATF1 and EWSR1/CREB1 chimeric transcripts in clear cell sarcoma (melanoma of soft parts).透明细胞肉瘤（软组织黑色素瘤）中EWSR1/ATF1和EWSR1/CREB1嵌合转录本的检测与特征分析。
Mod Pathol. 2009 Sep;22(9):1201-9. doi: 10.1038/modpathol.2009.85. Epub 2009 Jun 26.
7
EWSR1-POU5F1 fusion in soft tissue myoepithelial tumors. A molecular analysis of sixty-six cases, including soft tissue, bone, and visceral lesions, showing common involvement of the EWSR1 gene.EWSR1-POU5F1 融合基因在软组织肌上皮肿瘤中的表达。对 66 例软组织、骨和内脏病变的分子分析，显示 EWSR1 基因的常见累及。
Genes Chromosomes Cancer. 2010 Dec;49(12):1114-24. doi: 10.1002/gcc.20819.
8
DNA methylation profiling distinguishes Ewing-like sarcoma with EWSR1-NFATc2 fusion from Ewing sarcoma.DNA 甲基化分析可将具有 EWSR1-NFATc2 融合的尤文样肉瘤与尤文肉瘤区分开来。
J Cancer Res Clin Oncol. 2019 May;145(5):1273-1281. doi: 10.1007/s00432-019-02895-2. Epub 2019 Mar 20.
9
Malignant round cell tumor of bone with EWSR1-NFATC2 gene fusion.骨的恶性小圆细胞肿瘤伴 EWSR1-NFATC2 基因融合。
Virchows Arch. 2014 Aug;465(2):233-9. doi: 10.1007/s00428-014-1613-7. Epub 2014 Jul 4.
10
Expression of EWS-ETS fusions in NIH3T3 cells reveals significant differences to Ewing's sarcoma.EWS-ETS融合蛋白在NIH3T3细胞中的表达显示出与尤因肉瘤的显著差异。
Cell Cycle. 2006 Dec;5(23):2753-9. doi: 10.4161/cc.5.23.3505. Epub 2006 Dec 1.

引用本文的文献

1
Comprehensive analysis of E47‑like factors and verification of ELF4 in clear cell renal cell carcinoma.透明细胞肾细胞癌中E47样因子的综合分析及ELF4的验证
Oncol Lett. 2023 Jul 27;26(3):395. doi: 10.3892/ol.2023.13981. eCollection 2023 Sep.
2
EWSR1 prevents the induction of aneuploidy through direct regulation of Aurora B.EWSR1通过直接调控极光激酶B来防止非整倍体的诱导。
Front Cell Dev Biol. 2023 Feb 15;11:987153. doi: 10.3389/fcell.2023.987153. eCollection 2023.
3
A positive feedback circuit between RN7SK snRNA and mA readers is essential for tumorigenesis.

本文引用的文献

1
ELF5 isoform expression is tissue-specific and significantly altered in cancer.ELF5异构体的表达具有组织特异性，且在癌症中发生显著改变。
Breast Cancer Res. 2016 Jan 7;18(1):4. doi: 10.1186/s13058-015-0666-0.
2
A novel recurrent EP300-ZNF384 gene fusion in B-cell precursor acute lymphoblastic leukemia.B细胞前体急性淋巴细胞白血病中一种新的复发性EP300-ZNF384基因融合
Leukemia. 2015 Dec;29(12):2445-8. doi: 10.1038/leu.2015.111. Epub 2015 May 6.
3
Novel TNS3-MAP3K3 and ZFPM2-ELF5 fusion genes identified by RNA sequencing in multicystic mesothelioma with t(7;17)(p12;q23) and t(8;11)(q23;p13).
RN7SK snRNA 与 mA 读码器之间的正反馈回路对肿瘤发生至关重要。
Mol Ther. 2023 Jun 7;31(6):1615-1635. doi: 10.1016/j.ymthe.2022.12.013. Epub 2022 Dec 24.
4
Transcription Factors, R-Loops and Deubiquitinating Enzymes: Emerging Targets in Myelodysplastic Syndromes and Acute Myeloid Leukemia.转录因子、R环与去泛素化酶：骨髓增生异常综合征和急性髓系白血病中的新兴靶点
Cancers (Basel). 2021 Jul 26;13(15):3753. doi: 10.3390/cancers13153753.
5
Transcriptomic analysis identifies differences in gene expression in actinic keratoses after treatment with imiquimod and between responders and non responders.转录组分析鉴定了咪喹莫特治疗后光化性角化病和应答者与无应答者之间基因表达的差异。
Sci Rep. 2021 Apr 22;11(1):8775. doi: 10.1038/s41598-021-88424-z.
6
Nkx2.5 Functions as a Conditional Tumor Suppressor Gene in Colorectal Cancer Cells Acting as a Transcriptional Coactivator in p53-Mediated p21 Expression.Nkx2.5在结肠癌细胞中作为条件性肿瘤抑制基因发挥作用，在p53介导的p21表达中作为转录共激活因子。
Front Oncol. 2021 Apr 1;11:648045. doi: 10.3389/fonc.2021.648045. eCollection 2021.
7
Clinical presentation and differential splicing of SRSF2, U2AF1 and SF3B1 mutations in patients with acute myeloid leukemia.急性髓系白血病患者 SRSF2、U2AF1 和 SF3B1 突变的临床表现和差异剪接。
Leukemia. 2020 Oct;34(10):2621-2634. doi: 10.1038/s41375-020-0839-4. Epub 2020 May 1.
8
[Advances in the mouse models of myeloid leukemia].[髓系白血病小鼠模型的研究进展]
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2019 Oct 25;36(5):885-892. doi: 10.7507/1001-5515.201903012.
9
Expression of ELF5 in endometrial carcinoma tissues and its clinical significance.ELF5在子宫内膜癌组织中的表达及其临床意义。
Oncol Lett. 2018 Sep;16(3):3473-3480. doi: 10.3892/ol.2018.9093. Epub 2018 Jul 5.
10
[Screening and verification of key genes in T-cell acute lymphoblastic leukemia].[T细胞急性淋巴细胞白血病关键基因的筛选与验证]
Nan Fang Yi Ke Da Xue Xue Bao. 2018 Mar 20;38(3):261-267. doi: 10.3969/j.issn.1673-4254.2018.03.04.
通过RNA测序在伴有t(7;17)(p12;q23)和t(8;11)(q23;p13)的多囊性间皮瘤中鉴定出的新型TNS3-MAP3K3和ZFPM2-ELF5融合基因。
Cancer Lett. 2015 Feb 28;357(2):502-9. doi: 10.1016/j.canlet.2014.12.002. Epub 2014 Dec 4.
4
Sensitivity of SNX2-ABL1 toward tyrosine kinase inhibitors distinct from that of BCR-ABL1.SNX2-ABL1 对酪氨酸激酶抑制剂的敏感性与 BCR-ABL1 不同。
Leuk Res. 2014 Mar;38(3):361-70. doi: 10.1016/j.leukres.2013.11.017. Epub 2013 Dec 1.
5
Molecular detection and targeting of EWSR1 fusion transcripts in soft tissue tumors.软组织肿瘤中 EWSR1 融合转录本的分子检测与靶向治疗。
Med Oncol. 2013 Mar;30(1):412. doi: 10.1007/s12032-012-0412-8. Epub 2013 Jan 18.
6
Nmp4/CIZ closes the parathyroid hormone anabolic window.Nmp4/CIZ关闭甲状旁腺激素合成代谢窗口。
Crit Rev Eukaryot Gene Expr. 2012;22(3):205-18. doi: 10.1615/critreveukargeneexpr.v22.i3.40.
7
Functional studies of a novel germline p53 splicing mutation identified in a patient with Li-Fraumeni-like syndrome.在一位具有李-佛美尼综合征样特征的患者中鉴定到的新型种系 p53 剪接突变的功能研究。
Mol Carcinog. 2013 Oct;52(10):770-6. doi: 10.1002/mc.21912. Epub 2012 Apr 11.
8
Impairment of p53 acetylation by EWS-Fli1 chimeric protein in Ewing family tumors.EWS-Fli1 嵌合蛋白导致尤文家族肿瘤中 p53 乙酰化损伤。
Cancer Lett. 2012 Jul 1;320(1):14-22. doi: 10.1016/j.canlet.2012.01.018. Epub 2012 Jan 20.
9
Identification of the TAF15-ZNF384 fusion gene in two new cases of acute lymphoblastic leukemia with a t(12;17)(p13;q12).在两例伴有t(12;17)(p13;q12)的新急性淋巴细胞白血病病例中鉴定出TAF15-ZNF384融合基因。
Cancer Genet. 2011 Mar;204(3):147-52. doi: 10.1016/j.cancergen.2011.01.003.
10
MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers.MHC 类 II 转录激活物 CIITA 是淋巴癌中经常发生的基因融合伙伴。
Nature. 2011 Mar 17;471(7338):377-81. doi: 10.1038/nature09754. Epub 2011 Mar 2.