TP53 deletion as an MRD-dependent risk factor in childhood B-ALL: a post hoc analysis from a prospective cohort

TP53 deletion as an MRD-dependent risk factor in childhood B-ALL: a post hoc analysis from a prospective cohort | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article TP53 deletion as an MRD-dependent risk factor in childhood B-ALL: a post hoc analysis from a prospective cohort XIAOFAN ZHU, Yangyang Gao, Jun Li, Ning Wang, Wenbin An, Zixi Yin, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4337963/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The effect of TP53 alterations on childhood B-cell acute lymphoblastic leukemia (B-ALL) remains unclear. To investigate the impact of TP53 deletion ( TP53 del ) and TP53 mutation ( TP53 mut ) on prognosis, this post-hoc study used fluorescence in situ hybridization test to detect TP53 del in 914 newly diagnosed B-ALL children from a prospective Chinese Children’s Cancer Group ALL-2015 cohort. Targeted gene sequencing was used to identify TP53 mut in 345 out of the 914 patients. TP53 del was detected in 4.4% of cases. The frequency of hypodiploidy was higher in TP53 del subgroup (7.5% vs. 0.5%, P = 0.002), but patients with TP53 del were less likely to have other recurrent genetic abnormalities, including BCR::ABL1, ETV6::RUNX1, TCF3::PBX1 and MLL rearrangement. Univariable and multivariable analyses indicated that TP53 del was an independent risk factor for overall and disease-free survival. Furthermore, stratification analysis revealed that TP53 del was associated with adverse outcomes in patients with positive MRD after induction (0.0% vs. 58.2%, P < 0.001), suggesting an MRD-dependent pattern. But TP53 mut was not associated with poor survival (79.2% vs. 85.3%, P = 0.317). In summary, TP53 del may serve as a predictor for poor prognosis in pediatric B-ALL. Especially children in intermediate-risk group with positive MRD and TP53 del may deserve more aggressive treatment. Health sciences/Risk factors Health sciences/Diseases/Haematological diseases/Haematological cancer/Leukaemia/Acute lymphocytic leukaemia Full Text Additional Declarations Table 1 is available in the Supplementary Files section. Supplementary Files Table1.xlsx Table 1. Clinical characteristics of B-ALL children with or without TP53 del . *CNS involvement, central nervous system involvement, including CNS3, CNS2 or traumatic lumbar puncture 13 . Abbreviations: TP53 del , TP53 deletion; MLLr, MLL rearrangement; y, year. supplementarymaterial.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4337963","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":298426046,"identity":"284eb9c5-6996-4245-a42f-929c0fabc326","order_by":0,"name":"XIAOFAN 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12:50:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4337963/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4337963/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":57278336,"identity":"8b8994f6-168d-4653-9b93-5be7b236698a","added_by":"auto","created_at":"2024-05-28 14:19:09","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":430882,"visible":true,"origin":"","legend":"","description":"","filename":"TP53ALL.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4337963/v1_covered_c7476fbc-c1bc-4d5a-a7e4-515b32adb9a2.pdf"},{"id":56136030,"identity":"0b5edcf1-8525-46f3-aad6-7fbb981918cc","added_by":"auto","created_at":"2024-05-09 03:02:31","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":11750,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Clinical characteristics of B-ALL children with or without \u003cem\u003eTP53\u003c/em\u003e\u003csup\u003e\u003cem\u003edel\u003c/em\u003e\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e*CNS involvement, central nervous system involvement, including CNS3, CNS2 or traumatic lumbar puncture\u003csup\u003e13\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eAbbreviations: \u003cem\u003eTP53\u003c/em\u003e\u003csup\u003e\u003cem\u003edel\u003c/em\u003e\u003c/sup\u003e\u003cem\u003e, TP53\u003c/em\u003e deletion; \u003cem\u003eMLLr,\u003c/em\u003e \u003cem\u003eMLL\u003c/em\u003e rearrangement; y, year.\u003c/p\u003e","description":"","filename":"Table1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4337963/v1/1380addfba87f741abaf55c4.xlsx"},{"id":56135551,"identity":"322efacd-e7b8-4f6c-b34f-e282162bf9ee","added_by":"auto","created_at":"2024-05-09 02:54:31","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":227049,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"supplementarymaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-4337963/v1/8ba914af95ae49a22c107b88.docx"}],"financialInterests":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e","formattedTitle":"TP53 deletion as an MRD-dependent risk factor in childhood B-ALL: a post hoc analysis from a prospective cohort","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4337963/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4337963/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe effect of \u003cem\u003eTP53\u003c/em\u003e alterations on childhood B-cell acute lymphoblastic leukemia (B-ALL) remains unclear. To investigate the impact of \u003cem\u003eTP53\u003c/em\u003e deletion (\u003cem\u003eTP53\u003c/em\u003e\u003csup\u003e\u003cem\u003edel\u003c/em\u003e\u003c/sup\u003e) and TP53 mutation (\u003cem\u003eTP53\u003c/em\u003e\u003csup\u003e\u003cem\u003emut\u003c/em\u003e\u003c/sup\u003e) on prognosis, this post-hoc study used fluorescence in situ hybridization test to detect \u003cem\u003eTP53\u003c/em\u003e\u003csup\u003e\u003cem\u003edel\u003c/em\u003e\u003c/sup\u003e in 914 newly diagnosed B-ALL children from a prospective Chinese Children\u0026rsquo;s Cancer Group ALL-2015 cohort. Targeted gene sequencing was used to identify \u003cem\u003eTP53\u003c/em\u003e\u003csup\u003e\u003cem\u003emut\u003c/em\u003e\u003c/sup\u003e in 345 out of the 914 patients. \u003cem\u003eTP53\u003c/em\u003e\u003csup\u003e\u003cem\u003edel\u003c/em\u003e\u003c/sup\u003e was detected in 4.4% of cases. The frequency of hypodiploidy was higher in \u003cem\u003eTP53\u003c/em\u003e\u003csup\u003e\u003cem\u003edel\u003c/em\u003e\u003c/sup\u003e subgroup (7.5% vs. 0.5%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002), but patients with \u003cem\u003eTP53\u003c/em\u003e\u003csup\u003e\u003cem\u003edel\u003c/em\u003e\u003c/sup\u003e were less likely to have other recurrent genetic abnormalities, including \u003cem\u003eBCR::ABL1, ETV6::RUNX1, TCF3::PBX1 and MLL\u003c/em\u003e rearrangement. Univariable and multivariable analyses indicated that \u003cem\u003eTP53\u003c/em\u003e\u003csup\u003e\u003cem\u003edel\u003c/em\u003e\u003c/sup\u003e was an independent risk factor for overall and disease-free survival. Furthermore, stratification analysis revealed that \u003cem\u003eTP53\u003c/em\u003e\u003csup\u003e\u003cem\u003edel\u003c/em\u003e\u003c/sup\u003e was associated with adverse outcomes in patients with positive MRD after induction (0.0% vs. 58.2%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), suggesting an MRD-dependent pattern. But \u003cem\u003eTP53\u003c/em\u003e\u003csup\u003e\u003cem\u003emut\u003c/em\u003e\u003c/sup\u003e was not associated with poor survival (79.2% vs. 85.3%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.317). In summary, \u003cem\u003eTP53\u003c/em\u003e\u003csup\u003e\u003cem\u003edel\u003c/em\u003e\u003c/sup\u003e may serve as a predictor for poor prognosis in pediatric B-ALL. Especially children in intermediate-risk group with positive MRD and \u003cem\u003eTP53\u003c/em\u003e\u003csup\u003e\u003cem\u003edel\u003c/em\u003e\u003c/sup\u003e may deserve more aggressive treatment.\u003c/p\u003e","manuscriptTitle":"TP53 deletion as an MRD-dependent risk factor in childhood B-ALL: a post hoc analysis from a prospective cohort","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-09 02:54:17","doi":"10.21203/rs.3.rs-4337963/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1e366fe0-e7b7-455a-a819-e349f57a561c","owner":[],"postedDate":"May 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":31485289,"name":"Health sciences/Risk factors"},{"id":31485290,"name":"Health sciences/Diseases/Haematological diseases/Haematological cancer/Leukaemia/Acute lymphocytic leukaemia"}],"tags":[],"updatedAt":"2024-05-28T14:10:59+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-09 02:54:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4337963","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4337963","identity":"rs-4337963","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}