[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-417923-105":59,"doc-detail-417923-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","association-of-fibronectin-1-deregulation-with-tyrosine-kinase-inhibitor-resistance-in-chronic-myeloid-leukemia","Association of fibronectin 1 deregulation with tyrosine kinase inhibitor resistance in chronic myeloid leukemia","","Study centers on chronic myeloid leukemia (CML) and the problem of tyrosine kinase inhibitor (TKI) resistance, a key limitation despite high long-term survival from BCR::ABL1-targeted therapy. The work evaluates whether fibronectin 1 (FN1) deregulation contributes to resistance and can serve as a biomarker or target. FN1 mRNA/protein were measured by qPCR and immunoblotting, while adhesion and FN1 localization were assessed by Matrigel assays and immunofluorescence. Results show FN1 downregulation in resistant CML cells, where FN1 knockdown decreases susceptibility to multiple TKIs (including asciminib) and FN1 restoration re-sensitizes cells; FN1 deregulation is also seen in patient-derived peripheral blood.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/association-of-fibronectin-1-deregulation-with-tyrosine-kinase-inhibitor-resistance-in-chronic-myeloid-leukemia/417923/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/association-of-fibronectin-1-deregulation-with-tyrosine-kinase-inhibitor-resistance-in-chronic-myeloid-leukemia/417923.png","ImageObject",300,407,{"name":92,"@type":93},"Noah","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-05","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the study’s main goal regarding fibronectin 1 (FN1) in CML?","Question",{"text":112,"@type":113},"To gain deeper insights into the role of FN1 in chronic myeloid leukemia, especially in relation to TKI resistance.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do FN1 levels differ between TKI-resistant and TKI-sensitive CML cells?",{"text":117,"@type":113},"FN1 levels are significantly downregulated in CML cell lines resistant to BCR::ABL1 inhibitors in vitro.",{"name":119,"@type":110,"acceptedAnswer":120},"Does changing FN1 expression affect sensitivity to tyrosine kinase inhibitors?",{"text":121,"@type":113},"Yes. FN1 knockdown by siRNA reduces susceptibility to multiple TKIs, while restoring FN1 expression re-sensitizes TKI-resistant cells to TKI treatment.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},417923,1790766228,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},8796095462418,"https://ap-avatar.wpscdn.com/avatar/80000253c1241d02b47?x-image-process=image/resize,m_fixed,w_180,h_180&k=1778826106357471780","TYPE Original Research PUBLISHED 19 December 2025 DOI 10.3389/fcell.2025.1725857  \nOPEN ACCESS  \nEDITED BY  \nElham Vali Betts,  \nUniversity of California, Davis, United States  \nREVIEWED BY  \nDeepika Jayaprakash,  \nVanderbilt University, United States Shunjie Yu,  \nPeking University People’s Hospital, China  \n*CORRESPONDENCE  \nMeike Kaehler,  \n [kaehler@pharmakologie.uni-kiel.de](kaehler@pharmakologie.uni-kiel.de)  \nRECEIVED 15 October 2025  \nREVISED 17 November 2025  \nACCEPTED 08 December 2025  \nPUBLISHED 19 December 2025  \nCITATION  \nTiedemann L, Gorantla SP, Ahlf P, Schmidt LS, Pott C, Litterst M, Waetzig V, Nagel I, Ruemenapp J, von Bubnoff N, Cascorbi I and Kaehler M (2025) Association of fibronectin 1 deregulation with tyrosine kinase inhibitor resistance in chronic myeloid leukemia.  \nFront. Cell Dev. Biol. 13:1725857 .  \ndoi: 10.3389/fcell.2025.1725857  \nCOPYRIGHT  \n© 2025 Tiedemann, Gorantla, Ahlf, Schmidt, Pott, Litterst, Waetzig, Nagel, Ruemenapp, von Bubnoff, Cascorbi and Kaehler. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nAssociation of fibronectin  \n1 deregulation with tyrosine kinase inhibitor resistance in chronic myeloid leukemia  \nLina Tiedemann 1, Sivahari Prasad Gorantla 2, Philine Ahlf 1, Lucie Sophie Schmidt 1, Christiane Pott 3, Merit Litterst 1, Vicki Waetzig 1, Inga Nagel 4, Johanna Ruemenapp 5, Nikolas von Bubnoff 2, Ingolf Cascorbi 1 and Meike Kaehler 1*  \n1Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany, 2Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany, 3Second Medical Department, University Hospital SchleswigHolstein, Campus Kiel, Kiel, Germany, 4Institute of Human Genetics, University Hospital SchleswigHolstein, Campus Kiel, Kiel, Germany, 5Division of Neurological Pain Research and Therapy, Clinic for Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany  \nIntroduction: Therapy of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKIs) targeting the BCR::ABL1 kinase has become a paradigm for precision oncology. Despite the tremendous success of this strategy, with an overall long-term survival rate of 83%, approximately 25% of CML patients experience therapy failure within 5 years of treatment. TKI resistance is multifaceted, involving mutations in BCR::ABL1, but also BCR::ABL1-independent mechanisms. Among them, deregulation of cell adhesion and motility of CML cells has been observed in TKI-resistance. The extracellular matrix protein fibronectin 1 (FN1) has been shown to be deregulated in solid tumors promoting proliferation and metastasis. However, the role of FN1 in hematopoietic neoplasms remains to be fully elucidated. The aim of our study was to gain deeper insights into the role of FN1 .  \nMethods: FN1 mRNA and protein levels were analyzed using qPCR and immunoblotting. Transfection was performed using nucleofection or stable transfection, followed by analyses of cell number, proliferation and viability. Cell adhesion was assessed using Matrigel-coated surfaces, and FN1 localization was analyzed using immunofluorescence.  \nResults: FN1 levels were significantly downregulated in CML cell lines resistant against BCR::ABL1 inhibitors in vitro. SiRNA-mediated FN1 knockdown reduced the cell’s susceptibility to all generations of TKIs employed in treatment of CML, including asciminib. In contrast, the restoration of FN1 expression in TKI-resistant cells re-sensitized the cells to TKI treatment. This effect was also observed ","cbCaieIHXylb5cXV","https://ap.wps.com/l/cbCaieIHXylb5cXV","pdf",4019227,15,"English","# Introduction\n## Targeted therapy background in CML\n## Rationale for studying FN1 and resistance\n# Methods\n## FN1 expression analysis\n## Functional assays: proliferation, viability, adhesion\n# Results\n## FN1 downregulation in TKI-resistant CML cells\n## FN1 knockdown and restoration experiments\n## Clinical relevance in patient-derived samples\n# Conclusion","[{\"question\":\"What is the study’s main goal regarding fibronectin 1 (FN1) in CML?\",\"answer\":\"To gain deeper insights into the role of FN1 in chronic myeloid leukemia, especially in relation to TKI resistance.\"},{\"question\":\"How do FN1 levels differ between TKI-resistant and TKI-sensitive CML cells?\",\"answer\":\"FN1 levels are significantly downregulated in CML cell lines resistant to BCR::ABL1 inhibitors in vitro.\"},{\"question\":\"Does changing FN1 expression affect sensitivity to tyrosine kinase inhibitors?\",\"answer\":\"Yes. FN1 knockdown by siRNA reduces susceptibility to multiple TKIs, while restoring FN1 expression re-sensitizes TKI-resistant cells to TKI treatment.\"}]","Association of fibronectin 1 deregulation with tyrosine kinase inhibitor resistance in chronic myeloid leukemia | PDF",1790611203,38]