[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-500637-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-500637-en":130},{"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","the-role-of-il1rap-in-acute-myeloid-leukemia-chapter-2","The role of IL1RAP in acute myeloid leukemia - Chapter 2","","Upregulation of the plasma membrane receptor IL1RAP in Acute Myeloid Leukemia (AML) has been reported, but its function within the leukemic bone marrow niche remained unclear. This chapter examines IL1RAP-dependent signaling in AML versus normal hematopoiesis, linking high IL1RAP expression to a leukemic GMP-like state and showing IL1RAP knockdown reduces colony formation. IL1β triggered inflammatory secretomes via p38 MAPK and NFκB, affecting normal hematopoiesis through niche-mediated paracrine effects, reversible by Anakinra.",{"@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/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/the-role-of-il1rap-in-acute-myeloid-leukemia-chapter-2/500637/",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/the-role-of-il1rap-in-acute-myeloid-leukemia-chapter-2/500637.png","ImageObject",300,407,{"name":42,"@type":43},"McGucket","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-18","2026-10-03",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",7,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What role does IL1RAP play in acute myeloid leukemia?","Question",{"text":63,"@type":64},"IL1RAP upregulation is associated with a leukemic GMP-like state and supports AML-related signaling in the bone marrow niche. The chapter also links IL1RAP knockdown to reduced colony-forming capacity in AML.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does IL1β influence IL1RAP-expressing AML cells?",{"text":68,"@type":64},"Stimulation with IL1β induces multiple chemokines and an inflammatory secretome through p38 MAPK and NFκB pathways. However, IL1β-driven signaling was reported as dispensable for AML cell proliferation and NFκB-driven survival.",{"name":70,"@type":61,"acceptedAnswer":71},"Why is Anakinra relevant to IL1-IL1RAP signaling in AML?",{"text":72,"@type":64},"The IL1β-induced inflammatory secretome from IL1RAP-expressing AML cells affected normal hematopoiesis, including hematopoietic stem/progenitor cells, without directly increasing AML proliferation. 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Please check the document version below.  \nDocument Version  \nPublisher's PDF, also known as Version of record  \nPublication date: 2025  \nLink to publication in University of Groningen/UMCG research database  \nCitation for published version (APA):  \nSheveleva, S. (2025) . Dissecting the Molecular Landscape of Acute Myeloid Leukemia: From Inflammatory Niches to DNA Damage Responses. [Thesis fully internal (DIV), University of Groningen] . University of Groningen. [https://doi.org/10.33612/diss.1168049106](https://doi.org/10.33612/diss.1168049106)  \nCopyright  \nOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons) .  \nThe publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license. More information can be found on the University of Groningen website: [https://www.rug.nl/library/open-access/self-archiving-pure/taverne](https://www.rug.nl/library/open-access/self-archiving-pure/taverne)amendment.  \nTake-down policy  \nIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.  \nDownloaded from the University of Groningen/U MCG research database (Pure): [http://www.rug. nl/research/portal. For technical reasons the](http://www.rug. nl/research/portal. For technical reasons the)[ ](http://www.rug. nl/research/portal. For technical reasons the)[number of authors shown on this cover page is limited to 10 maximum.](number of authors shown on this cover page is limited to 10 maximum.)  \nDownload date: 03-10-2026  \nThe role of IL1RAP in acute myeloid leukemia  \nChapter 2  \nThe IL1-IL1RAP axis plays an important role in the inflammatory leukemic niche that favors acute myeloid leukemia proliferation over normal hematopoiesis  \nBauke de Boer\\# Sofia Sheveleva\\# Katja Apelt Edo Vellenga André B. Mulder Gerwin Huls  \nJan Jacob Schuringa  \n\\# equal contribution  \nHaematologica, 2021. 106: p. 3067-3078  \n2  \nAbstract  \nUpregulation of the plasma membrane receptor IL1RAP in Acute Myeloid Leukemia (AML) has been reported but its role in the context of the leukemic bone marrow niche is unclear. Here, we studied the signaling events downstream of IL1RAP in relation to leukemogenesis and normal hematopoiesis. High IL1RAP expression was associated with a leukemic GMP-like state, and knockdown of IL1RAP in AML reduced colony-forming capacity. Stimulation with IL1β resulted in the induction of multiple chemokines and an inflammatory secretome via thep38 MAPK and NFκB signaling pathways in IL1RAP-expressing AML cells, but IL1β-induced signaling was dispensable for AML cell proliferation and NFκBdriven survival. IL1RAP was also expressed in stromal cells where IL1β induced expression of inflammatory chemokines and cytokines as well. Intriguingly, the IL1β -induced inflammatory secretome of IL1RAP-expressing AML cells grown on astromal layer of mesenchymal stem cells affected normal hematopoiesis including hematopoietic stem/progenitor cells while AML cell proliferation was not affected. The addition of Anakinra, a Food and Drug Administration-approved IL1 receptor antagonist, could reverse this effect. Therefore, blocking the IL1-IL1RAP signaling axis might be a good therapeutic approach to reduce inflammation in the bone marrow niche and thereby promote normal hematopoietic recovery over AML proliferation after chemotherapy.  \nIntroduction  \nThe fate of both acute myeloid leukemia (AML) and normal hematopoietic stem cells ","cbCaie043ky7VmsA","https://ap.wps.com/l/cbCaie043ky7VmsA","pdf",11662102,41,"English","# Abstract\n# Introduction","[{\"question\":\"What role does IL1RAP play in acute myeloid leukemia?\",\"answer\":\"IL1RAP upregulation is associated with a leukemic GMP-like state and supports AML-related signaling in the bone marrow niche. The chapter also links IL1RAP knockdown to reduced colony-forming capacity in AML.\"},{\"question\":\"How does IL1β influence IL1RAP-expressing AML cells?\",\"answer\":\"Stimulation with IL1β induces multiple chemokines and an inflammatory secretome through p38 MAPK and NFκB pathways. However, IL1β-driven signaling was reported as dispensable for AML cell proliferation and NFκB-driven survival.\"},{\"question\":\"Why is Anakinra relevant to IL1-IL1RAP signaling in AML?\",\"answer\":\"The IL1β-induced inflammatory secretome from IL1RAP-expressing AML cells affected normal hematopoiesis, including hematopoietic stem/progenitor cells, without directly increasing AML proliferation. Adding Anakinra, an IL1 receptor antagonist, reversed this effect.\"}]","The role of IL1RAP in acute myeloid leukemia - Chapter 2 | PDF",1791013495,103]