[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-435326-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-435326-en":131},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","critical-role-of-niche-s100a8-for-acute-myeloid-leukemia-progression-and-hematopoiesis-regeneration","Critical role of niche S100A8 for acute myeloid leukemia progression and hematopoiesis regeneration","","Niche inflammation shaped by mesenchymal stromal cells (MSCs) critically governs acute myeloid leukemia (AML) behavior and stressed hematopoietic recovery. The study identifies S100A8 as dysregulated in AML MSCs and shows that increasing S100A8 enhances AML cell proliferation in vitro. In a murine MLL-AF9 AML model, S100A8 removal from MSCs prolongs survival and reduces leukemic infiltration while temporarily lowering HSC numbers but enabling long-term regeneration under stress.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/critical-role-of-niche-s100a8-for-acute-myeloid-leukemia-progression-and-hematopoiesis-regeneration/435326/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/critical-role-of-niche-s100a8-for-acute-myeloid-leukemia-progression-and-hematopoiesis-regeneration/435326.png","ImageObject",300,407,{"name":42,"@type":43},"Danger Angel","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-07","2026-09-29",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",15,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"How does MSC-derived S100A8 influence AML progression?","Question",{"text":63,"@type":64},"Upregulating S100A8 in MSCs increases AML cell proliferation in vitro. In addition, S100A8 binds Toll-like receptor 4 on leukemia cells and activates the PI3K/Akt signaling pathway.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What is the effect of deleting S100A8 in MSCs on hematopoietic stem cells under stress?",{"text":68,"@type":64},"Deleting S100A8 in MSCs causes a temporary decline in HSC numbers, but it facilitates long-term hematopoietic recovery under stress.",{"name":70,"@type":61,"acceptedAnswer":71},"How is S100A8 linked to the bone marrow microenvironment and hematopoietic support?",{"text":72,"@type":64},"S100A8 inhibits MSC differentiation into osteoblasts and reduces osteopontin expression, which is required for supporting HSCs.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},435326,1790928366,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":55,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145,"preview_page_count":4},962090769052,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","REGULAR ARTICLE  \nCritical role of niche S100A8 for acute myeloid leukemia progression and hematopoiesis regeneration  \nXiaoyan Liu,1,* Jinxian Wu,1,* Xinqi Li, 1,* Ruiyang Pan, 1 Li Liu,1 Tingting Huang, 1 Linlu Ma, 1 Guopeng Chen,1 Qian Wang,1 Nan Zhang,1 Xiqin Tong,1 Yuxin Tan,1 Hongqiang Jiang,1 Yuxing Liang, 1 Min Shen, 1 Ruihang Li, 1 Wanyue Yin,1 Xian Zhang, 1 and Fuling Zhou 1, 2 1 Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; and 2 School of Nursing, Research Center for Lifespan Health,  \nWuhan University, Wuhan, People’s Republic of China  \nKey Points  \n• MSC-derived S100A8 promotes AML progression by activating the PI3K/Akt signaling pathway through Toll-like receptor 4.  \n• S100A8 deletion in MSCs transiently reduces HSC numbers but enhances longterm hematopoietic regeneration under stress.  \nThe role of inflammation in regulating acute myeloid leukemia (AML) and stressed hematopoiesis is significant, although the molecular mechanisms are not fully understood. Here, we found that mesenchymal stromal cells (MSCs) had dysregulated expression of the inflammatory cytokine S100A8 in AML. Upregulating S100A8 in MSCs increased the proliferation of AML cells in vitro. In contrast, removing S100A8 from MSCs in the murine MLL-AF9 AML model resulted in longer survival and less infiltration of leukemia cells. S100A8 binds to the Toll-like receptor 4 on leukemia cells, activating the PI3K/Akt pathway. In addition, removing S100A8 from MSCs caused a temporary decline in hematopoietic stem cell (HSCs) numbers, but facilitated long-term hematopoietic recovery under stress. Furthermore, S100A8 inhibited MSC differentiation into osteoblasts and reduced the expression of osteopontin, which is required for supporting HSCs. Our findings highlight the importance of niche inflammation in promoting AML development while impeding hematopoietic regeneration.  \nIntroduction  \nHematopoietic stem cells (HSCs) establish themselves in a safe bone marrow (BM) environment composed of a complex, interconnected network of hematopoietic and nonhematopoietic cells that play critical roles in regulating HSC dormancy, proliferation, and migration.1 Under normal circumstances, hematopoiesis strikes a delicate balance between expansion and quiescence to achieve maximum production output.2,3 Both extrinsic 1 and intrinsic factors4 act hard to maintain this homeostasis while also allowing for adaptive responses5 and recovery6 in the face of emergencies such as chemotherapy and radiotherapy. Acute myeloid leukemia (AML) is a genetically heterogeneous disease characterized by clonal expansion of myeloid blasts evolved from hematopoietic stem and progenitor cells (HSPCs) .7 Adequate hematopoiesis regeneration under stress determines AML outcomes and is governed by BM HSC niche.8,9  \nSubmitted 2 January 2025; accepted 19 August 2025; prepublished online on Blood Advances First Edition 24 September 2025. [https://doi.org/10.1182/](https://doi.org/10.1182/)[ ](https://doi.org/10.1182/)[bloodadvances.2024015762](bloodadvances.2024015762.)[.](bloodadvances.2024015762.)  \n*X. Liu, J.W., and X. Li contributed equally to this study as joint first authors. The RNA sequencing data sets used in this study were reanalyzed from our previously published work. The raw data have been deposited in the National Center for Biotechnology Information Gene Expression Omnibus database (accession number GSE107814) .  \nThe data sets used and/or analyzed during this study are available on reasonable request from the corresponding authors, Fuling Zhou ([zhoufuling@whu.edu.cn](zhoufuling@whu.edu.cn)) and Xian Zhang ([sunshining1013@163.com](sunshining1013@163.com)).  \nThe full-text version of this article contains a data supplement.  \n© 2025 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercia","cbCaifIPhKKuBd5B","https://ap.wps.com/l/cbCaifIPhKKuBd5B","pdf",6079023,"English","# Key Points\n# Introduction\n# Role of MSC niche inflammation and S100A8","[{\"question\":\"How does MSC-derived S100A8 influence AML progression?\",\"answer\":\"Upregulating S100A8 in MSCs increases AML cell proliferation in vitro. In addition, S100A8 binds Toll-like receptor 4 on leukemia cells and activates the PI3K/Akt signaling pathway.\"},{\"question\":\"What is the effect of deleting S100A8 in MSCs on hematopoietic stem cells under stress?\",\"answer\":\"Deleting S100A8 in MSCs causes a temporary decline in HSC numbers, but it facilitates long-term hematopoietic recovery under stress.\"},{\"question\":\"How is S100A8 linked to the bone marrow microenvironment and hematopoietic support?\",\"answer\":\"S100A8 inhibits MSC differentiation into osteoblasts and reduces osteopontin expression, which is required for supporting HSCs.\"}]","Critical role of niche S100A8 for acute myeloid leukemia progression and hematopoiesis regeneration | PDF",1790672991,38]