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The study analyzes TP53 mutations across four myeloid subtypes—MDS, AML, AML-MRC, and therapy-related AML—identifying differences in mutation types, spectra, and hotspots versus solid tumors. Missense variants in the DNA-binding domain are most common, while inactivating and non–DNA-binding-domain mutations are more prevalent in AML-MRC than MDS. MDS mutations more often retain transcriptional activity, and co-mutation patterns differ by category and mutation type. Results indicate distinct roles for mutated TP53 in initiation and progression and support targeted identification of TP53 mutations in myeloid malignancies.",{"@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/comparison-of-tp53-mutations-in-myelodysplasia-and-acute-leukemia-suggests-divergent-roles-in-initiation-and-progression-380413/380413/",{"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/comparison-of-tp53-mutations-in-myelodysplasia-and-acute-leukemia-suggests-divergent-roles-in-initiation-and-progression-380413/380413.png","ImageObject",300,407,{"name":92,"@type":93},"Chumphorn","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What question does the study address about TP53 mutations?","Question",{"text":112,"@type":113},"It examines how specific TP53 mutations affect disease biology and whether these mechanisms differ across myeloid disease categories.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which myeloid subtypes were analyzed in the research?",{"text":117,"@type":113},"The study analyzed TP53 mutations in MDS, AML, AML with myelodysplasia-related changes (AML-MRC), and therapy-related acute myeloid leukemia (tAML).",{"name":119,"@type":110,"acceptedAnswer":120},"What main mutation-pattern differences were found between MDS and AML-MRC?",{"text":121,"@type":113},"Inactivating mutations and mutations outside the DNA-binding domain were more common in AML-MRC than in MDS, while TP53 mutations in MDS were more likely to retain transcriptional activity.","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},380413,1790247296,{"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":52,"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},2336475401981,"https://ap-avatar.wpscdn.com/avatar/22000c94efd8d5204d?x-image-process=image/resize,m_fixed,w_180,h_180&k=1786935347598174694","medRxiv preprint doi: [https://doi.org/10.1101/2023.09.04.23295042](https://doi.org/10.1101/2023.09.04.23295042); this version posted September 5, 2023. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.  \nIt is made available under a CC-BY-NC-ND 4.0 International license .  \n1 Comparison of TP53 Mutations in Myelodysplasia and Acute Leukemia Suggests Divergent  \n2 Roles in Initiation and Progression  \n3  \n4 Ashwini Jambhekar 1,2,*, Emily E. Ackerman 1, Berk A. Alpay3,4, Galit Lahav 1,2, and Scott B.  \n5 Lovitch5,* 6  \n7 1Department of Systems Biology, Harvard Medical School, Boston, MA  \n8 2Ludwig Center at Harvard, Boston, MA  \n9 3 Systems, Synthetic, and Quantitative Biology Program, Harvard University, Cambridge, MA  \n10 4Department of Organismal and Evolutionary Biology, Harvard University, Cambridge, MA  \n11 5Department of Pathology, Brigham and Women’s Hospital, Boston, MA  \n12 *Co-corresponding authors: [ashwini_jambhekar@hms.harvard.edu](ashwini_jambhekar@hms.harvard.edu), [slovitch@bwh.harvard.edu](slovitch@bwh.harvard.edu)[ ](slovitch@bwh.harvard.edu)13  \n14 Corresponding authors:  \n15 Ashwini Jambhekar, PhD  \n16 Department of Systems Biology  \n17 Harvard Medical School  \n18 210 Longwood Avenue, Armenise 605A  \n19 Boston, MA 02115  \n20 Phone: (617) 432-9091 21  \n22 Scott B. Lovitch, MD, PhD  \n23 Department of Pathology  \n24 Brigham and Women’s Hospital  \n25 75 Francis Street, Amory 3  \n26 Boston, MA 02115  \n27 Phone: (617) 525-9518  \n28 Fax: (844) 287-6275 29  \n30 Short title: TP53 Mutations in MDS and AML  \n31 The authors declare no potential conflicts of interest  \n1  \nNOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.  \nmedRxiv preprint doi: [https://doi.org/10.1101/2023.09.04.23295042](https://doi.org/10.1101/2023.09.04.23295042); this version posted September 5, 2023. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.  \nIt is made available under a CC-BY-NC-ND 4.0 International license .  \n32 Abstract 33  \n34 TP53 mutation predicts adverse prognosis in many cancers, including myeloid neoplasms, but  \n35 the mechanisms by which specific mutations impact disease biology, and whether they differ  \n36 between disease categories, remain unknown. We analyzed TP53 mutations in four myeloid  \n37 neoplasm subtypes (MDS, AML, AML with myelodysplasia-related changes (AML-MRC), and  \n38 therapy-related acute myeloid leukemia (tAML)), and identified differences in mutation types,  \n39 spectrum, and hotspots between disease categories and compared to solid tumors. Missense  \n40 mutations in the DNA-binding domain were most common across all categories, whereas  \n41 inactivating mutations and mutations outside the DNA binding domain were more common in  \n42 AML-MRC compared to MDS. TP53 mutations in MDS were more likely to retain  \n43 transcriptional activity, and co-mutation profiles were distinct between disease categories and  \n44 mutation types. Our findings suggest that mutated TP53 contributes to initiation and progression  \n45 of neoplasia via distinct mechanisms, and support the utility of specific identification of TP53  \n46 mutations in myeloid malignancies.  \n47  \nmedRxiv preprint doi: [https://doi.org/10.1101/2023.09.04.23295042](https://doi.org/10.1101/2023.09.04.23295042); this version posted September 5, 2023. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.  \nIt is made available under a CC-BY-NC-ND 4.0 International license .  \n48 Statement of Significance 49  \n50 The distribution and functional consequences of TP53 mutations differ between hematologic  \n51 ma","cbCaigBcDD1t4woy","https://ap.wps.com/l/cbCaigBcDD1t4woy","pdf",1820690,26,"English","# Abstract\n# Statement of Significance\n# Introduction","[{\"question\":\"What question does the study address about TP53 mutations?\",\"answer\":\"It examines how specific TP53 mutations affect disease biology and whether these mechanisms differ across myeloid disease categories.\"},{\"question\":\"Which myeloid subtypes were analyzed in the research?\",\"answer\":\"The study analyzed TP53 mutations in MDS, AML, AML with myelodysplasia-related changes (AML-MRC), and therapy-related acute myeloid leukemia (tAML).\"},{\"question\":\"What main mutation-pattern differences were found between MDS and AML-MRC?\",\"answer\":\"Inactivating mutations and mutations outside the DNA-binding domain were more common in AML-MRC than in MDS, while TP53 mutations in MDS were more likely to retain transcriptional activity.\"}]","Comparison of TP53 Mutations in Myelodysplasia and Acute Leukemia Suggests Divergent Roles in Initiation and Progression | PDF",1790240079,66]