• 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

Survivin 选择性调节人类白血病干细胞中失调的基因。

Survivin selectively modulates genes deregulated in human leukemia stem cells.

机构信息

Department of Pediatrics, Shimane University School of Medicine, 89-1 Enya-Cho, Izumo, Shimane 693-8501, Japan.

出版信息

J Oncol. 2011;2011:946936. doi: 10.1155/2011/946936. Epub 2010 Dec 23.

DOI:10.1155/2011/946936
PMID:21253548
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3021862/
Abstract

ITD-Flt3 mutations are detected in leukemia stem cells (LSCs) in acute myeloid leukemia (AML) patients. While antagonizing Survivin normalizes ITD-Flt3-induced acute leukemia, it also impairs hematopoietic stem cell (HSC) function, indicating that identification of differences in signaling pathways downstream of Survivin between LSC and HSC are crucial to develop selective Survivin-based therapeutic strategies for AML. Using a Survivin-deletion model, we identified 1,096 genes regulated by Survivin in ITD-Flt3-transformed c-kit(+), Sca-1(+), and lineage(neg) (KSL) cells, of which 137 are deregulated in human LSC. Of the 137, 124 genes were regulated by Survivin exclusively in ITD-Flt3(+) KSL cells but not in normal CD34(neg) KSL cells. Survivin-regulated genes in LSC connect through a network associated with the epidermal growth factor receptor signaling pathway and falls into various functional categories independent of effects on apoptosis. Pathways downstream of Survivin in LSC that are distinct from HSC can be potentially targeted for selective anti-LSC therapy.

摘要

ITD-Flt3 突变存在于急性髓系白血病（AML）患者的白血病干细胞（LSCs）中。拮抗 Survivin 可以使 ITD-Flt3 诱导的急性白血病正常化，但也会损害造血干细胞（HSC）的功能，这表明鉴定 Survivin 下游信号通路在 LSC 和 HSC 之间的差异对于开发针对 AML 的选择性 Survivin 为基础的治疗策略至关重要。我们使用 Survivin 缺失模型，鉴定了 1096 个在 ITD-Flt3 转化的 c-kit(+)、Sca-1(+)和谱系(neg)（KSL）细胞中受 Survivin 调节的基因，其中 137 个在人类 LSC 中失调。在 137 个基因中，有 124 个基因仅受 ITD-Flt3(+) KSL 细胞中的 Survivin 调节，而不受正常 CD34(neg) KSL 细胞的调节。LSC 中受 Survivin 调节的基因通过与表皮生长因子受体信号通路相关的网络连接，并分为各种与凋亡无关的功能类别。LSC 中与 HSC 不同的 Survivin 下游途径可能成为潜在的针对 LSC 的选择性治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ad2/3021862/fbf94e2a0a2d/JO2011-946936.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ad2/3021862/ca2ea6bddfb3/JO2011-946936.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ad2/3021862/67414261ad97/JO2011-946936.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ad2/3021862/cf451f79a15d/JO2011-946936.003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ad2/3021862/fbf94e2a0a2d/JO2011-946936.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ad2/3021862/ca2ea6bddfb3/JO2011-946936.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ad2/3021862/67414261ad97/JO2011-946936.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ad2/3021862/cf451f79a15d/JO2011-946936.003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ad2/3021862/fbf94e2a0a2d/JO2011-946936.004.jpg

相似文献

1
Survivin selectively modulates genes deregulated in human leukemia stem cells.Survivin 选择性调节人类白血病干细胞中失调的基因。
J Oncol. 2011;2011:946936. doi: 10.1155/2011/946936. Epub 2010 Dec 23.
2
Survivin mediates aberrant hematopoietic progenitor cell proliferation and acute leukemia in mice induced by internal tandem duplication of Flt3.生存素介导Flt3内部串联重复诱导的小鼠异常造血祖细胞增殖和急性白血病。
Blood. 2009 Jul 9;114(2):394-403. doi: 10.1182/blood-2008-11-188714. Epub 2009 May 1.
3
Immunoprofiling of leukemic stem cells CD34+/CD38-/CD123+ delineate FLT3/ITD-positive clones.白血病干细胞CD34+/CD38-/CD123+的免疫分析描绘出FLT3/ITD阳性克隆。
J Hematol Oncol. 2016 Jul 27;9(1):61. doi: 10.1186/s13045-016-0292-z.
4
Constitutive activation of Flt3 and STAT5A enhances self-renewal and alters differentiation of hematopoietic stem cells.Flt3和STAT5A的组成性激活增强了造血干细胞的自我更新能力并改变了其分化。
Exp Hematol. 2007 Apr;35(4 Suppl 1):105-16. doi: 10.1016/j.exphem.2007.01.018.
5
Single-cell mass cytometry reveals intracellular survival/proliferative signaling in FLT3-ITD-mutated AML stem/progenitor cells.单细胞质谱流式细胞术揭示了FLT3-ITD突变的急性髓系白血病干/祖细胞中的细胞内存活/增殖信号。
Cytometry A. 2015 Apr;87(4):346-56. doi: 10.1002/cyto.a.22628. Epub 2015 Jan 16.
6
FLT3-ITD up-regulates MCL-1 to promote survival of stem cells in acute myeloid leukemia via FLT3-ITD-specific STAT5 activation.FLT3-ITD 通过 FLT3-ITD 特异性 STAT5 激活上调 MCL-1 促进急性髓系白血病干细胞存活。
Blood. 2009 Dec 3;114(24):5034-43. doi: 10.1182/blood-2008-12-196055. Epub 2009 Oct 6.
7
Fms-related tyrosine kinase 3 expression discriminates hematopoietic stem cells subpopulations with differing engraftment-potential: identifying the most potent combination.Fms相关酪氨酸激酶3的表达可区分具有不同植入潜能的造血干细胞亚群：确定最有效的组合。
Transplantation. 2008 Apr 27;85(8):1175-84. doi: 10.1097/TP.0b013e31816a89cf.
8
Targeting of FLT3-ITD kinase contributes to high selectivity of imidazoacridinone C-1311 against FLT3-activated leukemia cells.靶向FLT3-ITD激酶有助于咪唑吖啶酮C-1311对FLT3激活的白血病细胞具有高选择性。
Biochem Pharmacol. 2015 Jun 15;95(4):238-52. doi: 10.1016/j.bcp.2015.04.006. Epub 2015 Apr 17.
9
Nuclear factor of activated T-cells, NFATC1, governs FLT3-driven hematopoietic stem cell transformation and a poor prognosis in AML.激活 T 细胞的核因子，NFATC1，调控 FLT3 驱动的造血干细胞转化和 AML 的不良预后。
J Hematol Oncol. 2019 Jul 8;12(1):72. doi: 10.1186/s13045-019-0765-y.
10
The effect of the detection of minimal residual disease for the prognosis and the choice of post-remission therapy of intermediate-risk acute myeloid leukemia without FLT3-ITD, NPM1 and biallelic CEBPA mutations.无 FLT3-ITD、NPM1 和双等位 CEBPA 突变的中危急性髓系白血病微小残留病检测对预后和缓解后治疗选择的影响。
Hematology. 2021 Dec;26(1):179-185. doi: 10.1080/16078454.2021.1880753.

引用本文的文献

1
Survivin enhances hippocampal neurogenesis and cognitive function in Alzheimer's disease mouse model.存活素增强阿尔茨海默病小鼠模型中的海马神经发生和认知功能。
CNS Neurosci Ther. 2024 Apr;30(4):e14509. doi: 10.1111/cns.14509. Epub 2023 Oct 30.
2
Emerging Importance of Survivin in Stem Cells and Cancer: the Development of New Cancer Therapeutics.**新兴的** **Survivin** **在干细胞和癌症中的重要性：新癌症治疗方法的发展**。
Stem Cell Rev Rep. 2020 Oct;16(5):828-852. doi: 10.1007/s12015-020-09995-4.
3
CXCR4 expression in the bone marrow microenvironment is required for hematopoietic stem and progenitor cell maintenance and early hematopoietic regeneration after myeloablation.

本文引用的文献

1
Emerging targeted therapies for breast cancer.乳腺癌的新兴靶向治疗方法。
J Clin Oncol. 2010 Jul 10;28(20):3366-79. doi: 10.1200/JCO.2009.25.4011. Epub 2010 Jun 7.
2
The molecular pathology of cancer.癌症的分子病理学。
Nat Rev Clin Oncol. 2010 May;7(5):251-65. doi: 10.1038/nrclinonc.2010.41. Epub 2010 Mar 30.
3
Proteomic and genetic approaches identify Syk as an AML target.蛋白质组学和遗传学方法确定脾酪氨酸激酶为急性髓系白血病的一个靶点。
CXCR4 在骨髓微环境中的表达对于造血干细胞和祖细胞的维持以及骨髓清除后早期造血的恢复是必需的。
Stem Cells. 2020 Jul;38(7):849-859. doi: 10.1002/stem.3174. Epub 2020 Mar 19.
4
FL118, a novel survivin inhibitor, wins the battle against drug-resistant and metastatic lung cancers through inhibition of cancer stem cell-like properties.新型存活素抑制剂FL118通过抑制癌症干细胞样特性，在对抗耐药性和转移性肺癌的战斗中取得胜利。
Am J Transl Res. 2017 Aug 15;9(8):3676-3686. eCollection 2017.
5
Aberrant RNA splicing and mutations in spliceosome complex in acute myeloid leukemia.急性髓系白血病中异常RNA剪接及剪接体复合物中的突变
Stem Cell Investig. 2017 Feb 9;4:6. doi: 10.21037/sci.2017.01.06. eCollection 2017.
6
Inhibition of serotonin receptor type 1 in acute myeloid leukemia impairs leukemia stem cell functionality: a promising novel therapeutic target.抑制急性髓系白血病中血清素受体 1 可损害白血病干细胞功能：一种有前途的新治疗靶点。
Leukemia. 2017 Nov;31(11):2288-2302. doi: 10.1038/leu.2017.52. Epub 2017 Feb 14.
7
Survivin: a unique target for tumor therapy.生存素：肿瘤治疗的独特靶点。
Cancer Cell Int. 2016 Jun 23;16:49. doi: 10.1186/s12935-016-0326-1. eCollection 2016.
8
Curcumin Enhanced Busulfan-Induced Apoptosis through Downregulating the Expression of Survivin in Leukemia Stem-Like KG1a Cells.姜黄素通过下调白血病干细胞样KG1a细胞中生存素的表达增强白消安诱导的细胞凋亡。
Biomed Res Int. 2015;2015:630397. doi: 10.1155/2015/630397. Epub 2015 Oct 18.
9
A novel small molecule FL118 that selectively inhibits survivin, Mcl-1, XIAP and cIAP2 in a p53-independent manner, shows superior antitumor activity.一种新型小分子 FL118，可选择性抑制存活素、Mcl-1、XIAP 和 cIAP2，且不依赖于 p53，具有优越的抗肿瘤活性。
PLoS One. 2012;7(9):e45571. doi: 10.1371/journal.pone.0045571. Epub 2012 Sep 19.
10
Genetic screen for regulators of lymph gland homeostasis and hemocyte maturation in Drosophila.在果蝇中筛选调控淋巴器官稳态和血细胞成熟的基因。
G3 (Bethesda). 2012 Mar;2(3):393-405. doi: 10.1534/g3.111.001693. Epub 2012 Mar 1.
Cancer Cell. 2009 Oct 6;16(4):281-94. doi: 10.1016/j.ccr.2009.08.018.
4
Survivin mediates aberrant hematopoietic progenitor cell proliferation and acute leukemia in mice induced by internal tandem duplication of Flt3.生存素介导Flt3内部串联重复诱导的小鼠异常造血祖细胞增殖和急性白血病。
Blood. 2009 Jul 9;114(2):394-403. doi: 10.1182/blood-2008-11-188714. Epub 2009 May 1.
5
Dysregulated gene expression networks in human acute myelogenous leukemia stem cells.人类急性髓系白血病干细胞中失调的基因表达网络。
Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3396-401. doi: 10.1073/pnas.0900089106. Epub 2009 Feb 13.
6
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.利用DAVID生物信息学资源对大型基因列表进行系统和综合分析。
Nat Protoc. 2009;4(1):44-57. doi: 10.1038/nprot.2008.211.
7
AML1/ETO-induced survivin expression inhibits transcriptional regulation of myeloid differentiation.AML1/ETO诱导的生存素表达抑制髓系分化的转录调控。
Exp Hematol. 2008 Nov;36(11):1449-60. doi: 10.1016/j.exphem.2008.05.008. Epub 2008 Aug 8.
8
Downregulation of survivin is associated with reductions in TNF receptors' mRNA and protein and alterations in nuclear factor kappa B signaling in urothelial cancer cells.生存素的下调与尿路上皮癌细胞中肿瘤坏死因子受体的mRNA和蛋白质减少以及核因子κB信号传导改变有关。
Cancer Invest. 2007 Dec;25(8):678-84. doi: 10.1080/07357900701600954.
9
Integration of biological networks and gene expression data using Cytoscape.使用Cytoscape整合生物网络与基因表达数据。
Nat Protoc. 2007;2(10):2366-82. doi: 10.1038/nprot.2007.324.
10
Erlotinib exhibits antineoplastic off-target effects in AML and MDS: a preclinical study.厄洛替尼在急性髓系白血病和骨髓增生异常综合征中表现出抗肿瘤脱靶效应：一项临床前研究。
Blood. 2008 Feb 15;111(4):2170-80. doi: 10.1182/blood-2007-07-100362. Epub 2007 Oct 9.