[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-367456-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-367456-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","tp53-mutated-myeloid-neoplasms-2024-update-on-diagnosis-risk-stratification-and-management","TP53-Mutated Myeloid Neoplasms - 2024 Update on Diagnosis, Risk-Stratification, and Management","","Alterations in the tumor suppressor gene TP53 are common across human cancers and are linked to aggressive behavior. About 8%–12% of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) carry TP53 mutations (TP53mut), producing major clinical challenges through intrinsic chemoresistance and poor outcomes. Standard approaches, including intensive chemotherapy, hypomethylating agents, and venetoclax, have not meaningfully improved survival. TP53mut myeloid neoplasms are now recognized as a distinct entity, but classification discrepancies can distort prognostic risk estimation. This review synthesizes new insights into biology, diagnosis, and treatment strategies, emphasizing limitations and unmet needs.",{"@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/tp53-mutated-myeloid-neoplasms-2024-update-on-diagnosis-risk-stratification-and-management/367456/",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/tp53-mutated-myeloid-neoplasms-2024-update-on-diagnosis-risk-stratification-and-management/367456.png","ImageObject",300,407,{"name":42,"@type":43},"Aria Callaghan","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-27","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",12,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"How common are TP53 mutations in MDS and AML, and why do they matter clinically?","Question",{"text":63,"@type":64},"TP53 mutations occur in roughly 8%–12% of MDS and AML cases. They drive aggressive disease behavior and major treatment challenges due to intrinsic chemoresistance and poor outcomes.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Why do current therapies fail to improve survival for TP53mut myeloid neoplasms meaningfully?",{"text":68,"@type":64},"Treatments used for other myeloid neoplasms, including intensive chemotherapy, hypomethylating agents, and venetoclax, do not translate into meaningful survival benefit for TP53mut patients. Development of multiple promising agents has also been discontinued due to lack of efficacy.",{"name":70,"@type":61,"acceptedAnswer":71},"How do the WHO-5 and International Consensus Classifications affect risk estimation?",{"text":72,"@type":64},"TP53mut myeloid neoplasms are recognized as a distinct entity in the 5th edition WHO and International Consensus Classifications. However, critical discrepancies between the two systems can lead to under- or overestimation of prognostic risk, complicating timely and effective management.","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},367456,1790610688,{"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":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146},962084926284,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","American Journal of Hematology  \n ANNUAL CLINICAL UPDATES IN HEMATOLOGICAL MALIGNANCIES  OPEN ACCESS   \nTP53-Mutated Myeloid Neoplasms: 2024 Update on Diagnosis, Risk-Stratification, and Management  \nMithun Vinod Shah1  | Daniel A. Arber2  | Devendra K. Hiwase3,4,5   \n1Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA | 2Department of Pathology, University of Chicago, Chicago, Illinois,  \nUSA | 3Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, South Australia, Australia | 4Precision Medicine Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia | 5Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia  \nCorrespondence: Mithun Vinod Shah ([shah.mithun@mayo.edu](shah.mithun@mayo.edu)) | Devendra K. Hiwase ([devendra.hiwase@sa.gov.au](devendra.hiwase@sa.gov.au))  \nReceived: 20 January 2025 | Revised: 25 February 2025 | Accepted: 27 February 2025  \nFunding: M.V.S. receives research funding to the institution from Astellas Pharma, AbbVie, KURA Oncology, Inc., Bristol Myers Squibb/Celgene, and Marker Therapeutics.  \nKeywords: AML—molecular diagnosis & therapy | myelodysplastic syndrome | neoplasia—myeloid leukemias and dysplasias | p53  \nABSTRACT  \nAlterations in the tumor suppressor gene TP53 are common in human cancers and are associated with an aggressive nature. Approximately 8%–12% of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) harbor TP53 mutations (TP53mut) and present immense challenges due to inherent chemoresistance and poor outcomes. As TP53mut are more common in older individuals and those with secondary/therapy-related myeloid neoplasms (MN), their incidence is expected to increase with an aging population and rising proportion of cancer survivors. Treatments used for other MN—intensive chemotherapy, hypomethylating agents, and the BCL-2 inhibitor venetoclax—do not improve the survival of TP53mut MN patients meaningfully. Additionally, further development of many promising agents has been discontinued, highlighting the challenges. Widespread acknowledgment of these problems led to the recognition of TP53mut MN as a distinct entity in the 5th edition of the World Health Organization and International Consensus Classifications. However, critical discrepancies between the two classifications may lead to under-or overestimation of the prognostic risk. Here, we review recent advances in the biology, diagnosis, and treatment of TP53mut MN. The development of TP53mut MN is positioned at the intersection of age, hereditary predisposition, and anticancer therapies. Precursor TP53mut clones can be detected years prior to the eventual leukemic transformation—raising the possibility of early intervention. We discuss the two classification systems and the bearing of the discrepancies between the two on timely and effective management. We provide novel evidence in the areas of discrepancies. Finally, we review the current therapeutic landscape and the obvious limitations of the currently used therapies.  \n1 | Introduction  \nAlterations in tumor suppressor gene TP53—the “guardian of the genome”—are the most prevalent abnormalities in human cancers and are generally associated with poor outcomes [1] . TP53 alterations are relatively uncommon in myeloid neoplasms (MN), accounting for 8%–10% of myelodysplastic syndrome (MDS) and 10%–12% of acute myeloid leukemia (AML)  \ncases [2–6] . Despite that, it remains a vexing challenge for three principal reasons: first, it is a highly aggressive leukemia with median survival of less than 1 year. Second, rapid advances in other types of MN have failed to translate into improved survival for this subset [7] . Effective treatments of TP53mut MN remain elusive, primarily due to the inherent chemorefractory nature [8–10]. Commonly employed treatments including intensive chemotherapies or hypomethylating agents (HMA) confer  \nThis is","cbCaigIQH1m8qJT2","https://ap.wps.com/l/cbCaigIQH1m8qJT2","pdf",4991563,28,"English","# Introduction\n# Challenges and clinical rationale\n# Classification systems and prognostic implications\n# Biology, diagnosis, and precursor lesions\n## Clonal hematopoiesis (CH)\n## Clonal cytopenia of undetermined significance (CCUS)\n# Therapeutic landscape and limitations","[{\"question\":\"How common are TP53 mutations in MDS and AML, and why do they matter clinically?\",\"answer\":\"TP53 mutations occur in roughly 8%–12% of MDS and AML cases. They drive aggressive disease behavior and major treatment challenges due to intrinsic chemoresistance and poor outcomes.\"},{\"question\":\"Why do current therapies fail to improve survival for TP53mut myeloid neoplasms meaningfully?\",\"answer\":\"Treatments used for other myeloid neoplasms, including intensive chemotherapy, hypomethylating agents, and venetoclax, do not translate into meaningful survival benefit for TP53mut patients. Development of multiple promising agents has also been discontinued due to lack of efficacy.\"},{\"question\":\"How do the WHO-5 and International Consensus Classifications affect risk estimation?\",\"answer\":\"TP53mut myeloid neoplasms are recognized as a distinct entity in the 5th edition WHO and International Consensus Classifications. However, critical discrepancies between the two systems can lead to under- or overestimation of prognostic risk, complicating timely and effective management.\"}]","TP53-Mutated Myeloid Neoplasms - 2024 Update on Diagnosis, Risk-Stratification, and Management | PDF",1790170856,71]