[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-378383-105":59,"doc-detail-378383-en":129},{"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":122,"head_meta":124,"extra_data":126,"updated_unix":128},105,"en","prl2-inhibition-elevates-pten-protein-and-ameliorates-progression-of-acute-myeloid-leukemia","PRL2 inhibition elevates PTEN protein and ameliorates progression of acute myeloid leukemia","","Overexpression of phosphatases of regenerating liver 2 (PRL2) is linked to worse outcomes in diverse cancers, in part by promoting PTEN degradation through tyrosine dephosphorylation. Acute myeloid leukemia (AML) frequently shows PRL2 upregulation together with reduced PTEN protein. A PTEN-knockdown AML animal model evaluated conditional PRL2 inhibition on PTEN protein levels and AML development. PRL2 inhibition increased median survival from 40 to over 60 weeks, delaying expansion of aberrantly differentiated hematopoietic stem cells and suppressing leukemia blast progression via increased PTEN and downregulated AKT/mTOR-regulated pathways.",{"@graph":69,"@context":121},[70,84,104],{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/prl2-inhibition-elevates-pten-protein-and-ameliorates-progression-of-acute-myeloid-leukemia/378383/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":98,"encodingFormat":97,"isAccessibleForFree":99,"interactionStatistic":100},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/prl2-inhibition-elevates-pten-protein-and-ameliorates-progression-of-acute-myeloid-leukemia/378383.png","ImageObject",300,407,{"name":92,"@type":93},"Mimi","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-24",true,{"@type":101,"interactionType":102,"userInteractionCount":8},"InteractionCounter",{"@type":103},"ViewAction",{"@type":105,"mainEntity":106},"FAQPage",[107,113,117],{"name":108,"@type":109,"acceptedAnswer":110},"What is the relationship between PRL2 and PTEN in cancer biology?","Question",{"text":111,"@type":112},"PRL2 catalyzes tyrosine dephosphorylation of PTEN, which promotes PTEN degradation and supports PRL2 oncogenic activity.","Answer",{"name":114,"@type":109,"acceptedAnswer":115},"How was the study modeled to test PRL2 inhibition in AML?",{"text":116,"@type":112},"The authors generated a PTEN-knockdown AML animal model to evaluate conditional PRL2 inhibition on PTEN protein and AML development and progression.",{"name":118,"@type":109,"acceptedAnswer":119},"What was the impact of PRL2 inhibition on survival and leukemia progression?",{"text":120,"@type":112},"PRL2 inhibition significantly increased median survival from 40 weeks to greater than 60 weeks and suppressed leukemia blast progression.","https://schema.org",{"og:url":83,"og:type":123,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":125,"canonical":83},"index,follow",{"doc_id":127,"site_id":62},378383,1790269650,{"code":4,"msg":5,"data":130},{"doc_id":127,"user_id":131,"nickname":92,"user_avatar":132,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"language":138,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":139,"faqs":140,"seo_title":141,"seo_description":67,"update_tm":142,"read_time":143},2336477974920,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","RESE AR CH  \nARTICLE  \nConflict of interest: The authors have declared that no conflict of interest exists.  \nCopyright: © 2023, Carlock et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.  \nSubmitted: February 27, 2023  \nAccepted: August 23, 2023  \nPublished: October 9, 2023  \nReference information: JCI Insight. 2023;8(19):e170065 .  \n[https://doi.org/10.1172/jci](https://doi.org/10.1172/jci). insight.170065 .  \nPRL2 inhibition elevates PTEN protein and ameliorates progression of acute myeloid leukemia  \nColin Carlock,1 Yunpeng Bai,2 Allison Paige-Hood,3 Qinglin Li,2 Frederick Nguele Meke,2 and Zhong-Yin Zhang2,4,5,6  \n1Department of Biochemistry, 2Department of Medicinal Chemistry and Molecular Pharmacology, 3Department of Biological Sciences, 4Department of Chemistry, 5Institute for Cancer Research, and 6Institute for Drug Discovery, Purdue University, West Lafayette, Indiana, USA.  \nOverexpression of phosphatases of regenerating liver 2 (PRL2), detected in numerous diverse cancers, is often associated with increased severity and poor patient prognosis. PRL2-catalyzed tyrosine dephosphorylation of the tumor suppressor PTEN results in increased PTEN degradation and has been identified as a mechanism underlying PRL2 oncogenic activity. Overexpression of PRL2, coincident with reduced PTEN protein, is frequently observed in patients with acute myeloid leukemia (AML). In the current study, a PTEN-knockdown AML animal model was generated to assess the effect of conditional PRL2 inhibition on the level of PTEN protein and the development and progression of AML. Inhibition of PRL2 resulted in a significant increase in median animal survival, from 40 weeks to greater than 60 weeks. The prolonged survival reflected delayed expansion of aberrantly differentiated hematopoietic stem cells into leukemia blasts, resulting in extended time required for clinically relevant leukemia blast accumulation in the BM niche. Leukemia blast suppression following PRL2 inhibition was correlated with an increase in PTENand downregulation of AKT/mTOR-regulated pathways. These observations directly established, in a disease model, the viability of PRL2 inhibition as a therapeutic strategy for improving clinical outcomes in AML and potentially other PTEN-deficient cancers by slowing cancer progression.  \nIntroduction  \nPrecise regulation of protein tyrosine phosphorylation is essential for maintaining cellular homeostasis. The importance of protein tyrosine kinases (PTKs) in regulating cellular signaling is well established; however, the role of protein tyrosine phosphatases (PTPs) in reversing or blocking kinase-activated signaling cascades is not yet fully appreciated (1) . Increasing evidence supports a critical role of PTPs in the pathogenesis of many diseases, such as the identification of numerous PTPs as potential oncogenes and tumor suppressors (2) . Understanding the functional role of PTPs in disease has been hampered by poorly defined PTP substrate specificity and a lack of identified biological targets.  \nThe phosphatases of regenerating liver (PRL) is a 3-member PTP subfamily, composed of PTP4A1 (PRL1), PTP4A2 (PRL2), and PTP4A3 (PRL3), that shares substantial amino acid sequence homology (3) . Overexpression of the PRLs has been associated with many types of human cancer and is frequently prognostic of worsened patient outcomes (4–6) . However, the mechanisms by which the PRLs contribute to tumorigenesis are poorly understood, and both catalytic and noncatalytic roles for PRLs have been proposed (5, 7) . Recently, the tumor suppressor protein PTEN was identified as a PRL2 substrate (7) . PTENis frequently downregulated in cancer, resulting in activation of the PI3K/AKT/mTOR pathway and consequent enhanced cell growth and proliferation (8) . PRL2 was demonstrated to dephosphorylate PTEN atthe Y336 residue, resulting in increased NEDD4-mediated polyubiquitination and su","cbCaib4LDYx9XTDm","https://ap.wps.com/l/cbCaib4LDYx9XTDm","pdf",3600391,"English","# Introduction\n## Protein tyrosine phosphorylation and phosphatases in disease\n## PRL family, PTEN regulation, and proposed mechanisms\n## Acute myeloid leukemia context and PTEN deficiency","[{\"question\":\"What is the relationship between PRL2 and PTEN in cancer biology?\",\"answer\":\"PRL2 catalyzes tyrosine dephosphorylation of PTEN, which promotes PTEN degradation and supports PRL2 oncogenic activity.\"},{\"question\":\"How was the study modeled to test PRL2 inhibition in AML?\",\"answer\":\"The authors generated a PTEN-knockdown AML animal model to evaluate conditional PRL2 inhibition on PTEN protein and AML development and progression.\"},{\"question\":\"What was the impact of PRL2 inhibition on survival and leukemia progression?\",\"answer\":\"PRL2 inhibition significantly increased median survival from 40 weeks to greater than 60 weeks and suppressed leukemia blast progression.\"}]","PRL2 inhibition elevates PTEN protein and ameliorates progression of acute myeloid leukemia | PDF",1790229697,48]