• 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

间充质龛重塑通过施万氏钙素 1 损害急性髓系白血病中的造血功能。

Mesenchymal niche remodeling impairs hematopoiesis via stanniocalcin 1 in acute myeloid leukemia.

机构信息

Haematopoietic Stem Cell Laboratory, Francis Crick Institute, London, United Kingdom.

Haemato-Oncology Unit, Royal Marsden Hospital, Institute of Cancer Research, London, United Kingdom.

出版信息

J Clin Invest. 2020 Jun 1;130(6):3038-3050. doi: 10.1172/JCI133187.

DOI:10.1172/JCI133187
PMID:32364536
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7260026/
Abstract

Acute myeloid leukemia (AML) disrupts the generation of normal blood cells, predisposing patients to hemorrhage, anemia, and infections. Differentiation and proliferation of residual normal hematopoietic stem and progenitor cells (HSPCs) are impeded in AML-infiltrated bone marrow (BM). The underlying mechanisms and interactions of residual hematopoietic stem cells (HSCs) within the leukemic niche are poorly understood, especially in the human context. To mimic AML infiltration and dissect the cellular crosstalk in human BM, we established humanized ex vivo and in vivo niche models comprising AML cells, normal HSPCs, and mesenchymal stromal cells (MSCs). Both models replicated the suppression of phenotypically defined HSPC differentiation without affecting their viability. As occurs in AML patients, the majority of HSPCs were quiescent and showed enrichment of functional HSCs. HSPC suppression was largely dependent on secreted factors produced by transcriptionally remodeled MSCs. Secretome analysis and functional validation revealed MSC-derived stanniocalcin 1 (STC1) and its transcriptional regulator HIF-1α as limiting factors for HSPC proliferation. Abrogation of either STC1 or HIF-1α alleviated HSPC suppression by AML. This study provides a humanized model to study the crosstalk among HSPCs, leukemia, and their MSC niche, and a molecular mechanism whereby AML impairs normal hematopoiesis by remodeling the mesenchymal niche.

摘要

急性髓系白血病 (AML) 会破坏正常血细胞的生成，使患者容易出现出血、贫血和感染。浸润性骨髓中的剩余正常造血干/祖细胞 (HSPCs) 的分化和增殖受到阻碍。AML 浸润骨髓中剩余造血干细胞 (HSCs) 的潜在机制和相互作用在人类背景下还知之甚少。为了模拟 AML 浸润并剖析人类 BM 中的细胞串扰，我们建立了包含 AML 细胞、正常 HSPCs 和间充质基质细胞 (MSCs) 的人源化体外和体内生态位模型。这两种模型都复制了表型定义的 HSPC 分化受到抑制，而不影响其活力的现象。与 AML 患者一样，大多数 HSPCs 处于静止状态，并显示出功能 HSCs 的富集。HSPC 的抑制在很大程度上取决于转录重编程的 MSC 产生的分泌因子。分泌组分析和功能验证表明 MSC 衍生的 STC1（STC1）及其转录调节剂 HIF-1α 是 HSPC 增殖的限制因素。STC1 或 HIF-1α 的缺失减轻了 AML 对 HSPC 的抑制作用。本研究提供了一种人源化模型，用于研究 HSPCs、白血病及其 MSC 生态位之间的串扰，以及 AML 通过重塑间充质生态位来损害正常造血的分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0339/7260026/888d13fd634e/jci-130-133187-g091.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0339/7260026/0ab6ebcd20b9/jci-130-133187-g085.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0339/7260026/25a570abf14f/jci-130-133187-g086.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0339/7260026/90897c30b341/jci-130-133187-g087.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0339/7260026/48dfe1919a4f/jci-130-133187-g088.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0339/7260026/fecdebf4da9c/jci-130-133187-g089.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0339/7260026/373da4cb5202/jci-130-133187-g090.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0339/7260026/888d13fd634e/jci-130-133187-g091.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0339/7260026/0ab6ebcd20b9/jci-130-133187-g085.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0339/7260026/25a570abf14f/jci-130-133187-g086.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0339/7260026/90897c30b341/jci-130-133187-g087.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0339/7260026/48dfe1919a4f/jci-130-133187-g088.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0339/7260026/fecdebf4da9c/jci-130-133187-g089.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0339/7260026/373da4cb5202/jci-130-133187-g090.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0339/7260026/888d13fd634e/jci-130-133187-g091.jpg

相似文献

1
Mesenchymal niche remodeling impairs hematopoiesis via stanniocalcin 1 in acute myeloid leukemia.间充质龛重塑通过施万氏钙素 1 损害急性髓系白血病中的造血功能。
J Clin Invest. 2020 Jun 1;130(6):3038-3050. doi: 10.1172/JCI133187.
2
Acute myeloid leukemia transforms the bone marrow niche into a leukemia-permissive microenvironment through exosome secretion.急性髓系白血病通过外泌体分泌将骨髓龛转变为白血病易感性的微环境。
Leukemia. 2018 Mar;32(3):575-587. doi: 10.1038/leu.2017.259. Epub 2017 Aug 17.
3
Stanniocalcin 1 is overexpressed in multipotent mesenchymal stromal cells from acute myeloid leukemia patients.Stanniocalcin 1 在急性髓系白血病患者的多能间充质基质细胞中过表达。
Hematology. 2021 Dec;26(1):565-576. doi: 10.1080/16078454.2021.1962048.
4
Mesenchymal COX2-PG secretome engages NR4A-WNT signalling axis in haematopoietic progenitors to suppress anti-leukaemia immunity.间充质 COX2-PG 分泌组通过 NR4A-WNT 信号轴作用于造血祖细胞抑制抗白血病免疫。
Br J Haematol. 2018 Nov;183(3):445-456. doi: 10.1111/bjh.15548. Epub 2018 Aug 14.
5
Leukemia cells impair normal hematopoiesis and induce functionally loss of hematopoietic stem cells through immune cells and inflammation.白血病细胞通过免疫细胞和炎症损害正常造血，并导致造血干细胞功能丧失。
Leuk Res. 2018 Feb;65:49-54. doi: 10.1016/j.leukres.2018.01.002. Epub 2018 Jan 2.
6
Mesenchymal stromal cells from patients with acute myeloid leukemia have altered capacity to expand differentiated hematopoietic progenitors.急性髓系白血病患者的间充质基质细胞在扩增分化造血祖细胞方面的能力发生了改变。
Leuk Res. 2015 Apr;39(4):486-93. doi: 10.1016/j.leukres.2015.01.013. Epub 2015 Feb 2.
7
Hypoxia-CXCL6 axis affects arteriolar niche remodeling in acute myeloid leukemia.缺氧-CXCL6 轴影响急性髓系白血病中的小动脉龛重塑。
Exp Biol Med (Maywood). 2021 Jan;246(1):84-96. doi: 10.1177/1535370220960675. Epub 2020 Nov 9.
8
Adipogenic Mesenchymal Stromal Cells from Bone Marrow and Their Hematopoietic Supportive Role: Towards Understanding the Permissive Marrow Microenvironment in Acute Myeloid Leukemia.骨髓间充质基质细胞的成脂分化及其对造血的支持作用：浅析急性髓系白血病中允许性骨髓微环境。
Stem Cell Rev Rep. 2016 Apr;12(2):235-44. doi: 10.1007/s12015-015-9639-z.
9
Targeting the plasticity of mesenchymal stromal cells to reroute the course of acute myeloid leukemia.靶向间充质基质细胞的可塑性以改变急性髓系白血病的病程。
Blood. 2021 Aug 19;138(7):557-570. doi: 10.1182/blood.2020009845.
10
Abnormal adipogenic signaling in the bone marrow mesenchymal stem cells contributes to supportive microenvironment for leukemia development.骨髓间充质干细胞中的异常脂肪生成信号传导有助于白血病发展的支持性微环境。
Cell Commun Signal. 2023 Oct 10;21(1):277. doi: 10.1186/s12964-023-01231-z.

引用本文的文献

1
Bridging the marrow: a co-culture-platform of leukemia cells and MS5-derived stromal cells or adipocytes.连接骨髓：白血病细胞与MS5来源的基质细胞或脂肪细胞的共培养平台。
Cell Death Discov. 2025 Aug 5;11(1):366. doi: 10.1038/s41420-025-02631-5.
2
Expression of Aldehyde Dehydrogenase 1A1 in Relapse-Associated Cells in Acute Myeloid Leukemia.醛脱氢酶1A1在急性髓系白血病复发相关细胞中的表达
Cells. 2025 Jul 7;14(13):1038. doi: 10.3390/cells14131038.
3
MMP14 from BM-MSCs facilitates progression and Ara-C resistance in acute myeloid leukemia via the JAK/STAT pathway.

本文引用的文献

1
A Cellular Taxonomy of the Bone Marrow Stroma in Homeostasis and Leukemia.骨髓基质细胞在稳态和白血病中的细胞分类学
Cell. 2019 Jun 13;177(7):1915-1932.e16. doi: 10.1016/j.cell.2019.04.040. Epub 2019 May 23.
2
The bone marrow microenvironment at single-cell resolution.单细胞分辨率下的骨髓微环境。
Nature. 2019 May;569(7755):222-228. doi: 10.1038/s41586-019-1104-8. Epub 2019 Apr 10.
3
Distinct roles of mesenchymal stem and progenitor cells during the development of acute myeloid leukemia in mice.间充质干细胞和祖细胞在小鼠急性髓系白血病发展过程中的不同作用。
来自骨髓间充质干细胞的基质金属蛋白酶14通过JAK/STAT信号通路促进急性髓系白血病的进展并导致阿糖胞苷耐药。
Exp Hematol Oncol. 2025 Mar 22;14(1):43. doi: 10.1186/s40164-025-00635-6.
4
Unlocking reproducible transcriptomic signatures for acute myeloid leukaemia: Integration, classification and drug repurposing.解锁急性髓系白血病可重现的转录组学特征：整合、分类和药物再利用。
J Cell Mol Med. 2024 Sep;28(17):e70085. doi: 10.1111/jcmm.70085.
5
CircUBA2 promotes the cancer stem cell-like properties of gastric cancer through upregulating STC1 via sponging miR-144-5p.环状泛素样修饰激活酶2通过海绵吸附微小RNA-144-5p上调激肽释放酶抑制因子1，从而促进胃癌的癌症干细胞样特性。
Cancer Cell Int. 2024 Aug 5;24(1):276. doi: 10.1186/s12935-024-03423-0.
6
Leukemic Stem Cells and Hematological Malignancies.白血病干细胞与血液系统恶性肿瘤
Int J Mol Sci. 2024 Jun 17;25(12):6639. doi: 10.3390/ijms25126639.
7
rhBMP-2 induces terminal differentiation of human bone marrow mesenchymal stromal cells only by synergizing with other signals.rhBMP-2 仅通过与其他信号协同作用诱导人骨髓间充质基质细胞的终末分化。
Stem Cell Res Ther. 2024 Apr 29;15(1):124. doi: 10.1186/s13287-024-03735-y.
8
Molecular characterization of Golgi apparatus-related genes indicates prognosis and immune infiltration in osteosarcoma.高尔基器相关基因的分子特征表明骨肉瘤的预后和免疫浸润。
Aging (Albany NY). 2024 Mar 7;16(6):5249-5263. doi: 10.18632/aging.205645.
9
Preliminary delivery efficiency prediction of nanotherapeutics into crucial cell populations in bone marrow niche.纳米治疗药物向骨髓微环境中关键细胞群体的初步递送效率预测
Asian J Pharm Sci. 2023 Nov;18(6):100868. doi: 10.1016/j.ajps.2023.100868. Epub 2023 Nov 19.
10
Abnormal adipogenic signaling in the bone marrow mesenchymal stem cells contributes to supportive microenvironment for leukemia development.骨髓间充质干细胞中的异常脂肪生成信号传导有助于白血病发展的支持性微环境。
Cell Commun Signal. 2023 Oct 10;21(1):277. doi: 10.1186/s12964-023-01231-z.
Blood Adv. 2018 Jun 26;2(12):1480-1494. doi: 10.1182/bloodadvances.2017013870.
4
An ERK-Dependent Feedback Mechanism Prevents Hematopoietic Stem Cell Exhaustion.ERK 依赖性反馈机制可防止造血干细胞衰竭。
Cell Stem Cell. 2018 Jun 1;22(6):879-892.e6. doi: 10.1016/j.stem.2018.05.003. Epub 2018 May 24.
5
Transforming growth factor β1-mediated functional inhibition of mesenchymal stromal cells in myelodysplastic syndromes and acute myeloid leukemia.转化生长因子 β1 介导的骨髓增生异常综合征和急性髓系白血病间充质基质细胞功能抑制。
Haematologica. 2018 Sep;103(9):1462-1471. doi: 10.3324/haematol.2017.186734. Epub 2018 May 17.
6
Niches for Hematopoietic Stem Cells and Their Progeny.造血干细胞及其后代的龛位。
Immunity. 2018 Apr 17;48(4):632-648. doi: 10.1016/j.immuni.2018.03.024.
7
Proliferation dynamics of acute myeloid leukaemia and haematopoietic progenitors competing for bone marrow space.急性髓系白血病与争夺骨髓空间的造血祖细胞的增殖动力学
Nat Commun. 2018 Feb 6;9(1):519. doi: 10.1038/s41467-017-02376-5.
8
Megakaryocyte-derived excessive transforming growth factor β1 inhibits proliferation of normal hematopoietic stem cells in acute myeloid leukemia.巨核细胞衍生的过量转化生长因子β1抑制急性髓系白血病中正常造血干细胞的增殖。
Exp Hematol. 2018 Apr;60:40-46.e2. doi: 10.1016/j.exphem.2017.12.010. Epub 2018 Jan 4.
9
Acute myeloid leukaemia disrupts endogenous myelo-erythropoiesis by compromising the adipocyte bone marrow niche.急性髓系白血病通过破坏脂肪细胞骨髓龛来扰乱内源性骨髓造血。
Nat Cell Biol. 2017 Nov;19(11):1336-1347. doi: 10.1038/ncb3625. Epub 2017 Oct 16.
10
Increased Vascular Permeability in the Bone Marrow Microenvironment Contributes to Disease Progression and Drug Response in Acute Myeloid Leukemia.骨髓微环境中血管通透性增加促进急性髓系白血病的疾病进展和药物反应。
Cancer Cell. 2017 Sep 11;32(3):324-341.e6. doi: 10.1016/j.ccell.2017.08.001. Epub 2017 Sep 1.