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Identification of novel DNA methylation prognostic biomarkers for AML with normal cytogenetics

dc.contributor.authorCardoso, Cândida
dc.contributor.authorPestana, Daniel
dc.contributor.authorGokuladhas, Sreemol
dc.contributor.authorMarreiros, Ana
dc.contributor.authorJustin M. O'Sullivan
dc.contributor.authorBinnie, Alexandra
dc.contributor.authorTeotónio Fernandes, Mónica Alexandra
dc.contributor.authorCastelo-Branco, Pedro
dc.date.accessioned2024-10-03T10:59:09Z
dc.date.available2024-10-03T10:59:09Z
dc.date.issued2024-07
dc.description.abstractPURPOSE AML is a hematologic cancer that is clinically heterogeneous, with a wide range of clinical outcomes. DNA methylation changes are a hallmark of AML but are not routinely used as a criterion for risk stratification. The aim of this study was to explore DNA methylation markers that could risk stratify patients with cytogenetically normal AML (CN-AML), currently classified as intermediate-risk.MATERIALS AND METHODSDNA methylation profiles in whole blood samples from 77 patients with CN-AML in The Cancer Genome Atlas (LAML cohort) were analyzed. Individual 5'-cytosine-phosphate-guanine-3' (CpG) sites were assessed for their ability to predict overall survival. The output was validated using DNA methylation profiles from bone marrow samples of 79 patients with CN-AML in a separate data set from the Gene Expression Omnibus.RESULTSIn the training set, using DNA methylation data derived from the 450K array, we identified 2,549 CpG sites that could potentially distinguish patients with CN-AML with an adverse prognosis (intermediate-poor) from those with a more favorable prognosis (intermediate-favorable) independent of age. Of these, 25 CpGs showed consistent prognostic potential across both the 450K and 27K array platforms. In a separate validation data set, nine of these 25 CpGs exhibited statistically significant differences in 2-year survival. These nine validated CpGs formed the basis for a combined prognostic biomarker panel, which includes an 8-CpG Somatic Panel and the methylation status of cg23947872. This panel displayed strong predictive ability for 2-year survival, 2-year progression-free survival, and complete remission in the validation cohort.CONCLUSIONThis study highlights DNA methylation profiling as a promising approach to enhance risk stratification in patients with CN-AML, potentially offering a pathway to more personalized treatment strategies.eng
dc.identifier.doi10.1200/cci.23.00265
dc.identifier.issn2473-4276
dc.identifier.urihttp://hdl.handle.net/10400.1/25988
dc.language.isoeng
dc.peerreviewedyes
dc.publisherAmerican Society of Clinical Oncology (ASCO)
dc.relation.ispartofJCO Clinical Cancer Informatics
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleIdentification of novel DNA methylation prognostic biomarkers for AML with normal cytogeneticseng
dc.typejournal article
dspace.entity.typePublication
oaire.citation.startPagee2300265
oaire.citation.titleJCO Clinical Cancer Informatics
oaire.citation.volume8
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameCardoso
person.familyNamePestana
person.familyNameMarreiros
person.familyNameBinnie
person.familyNameTeotónio Fernandes
person.familyNameCastelo-Branco
person.givenNameCândida
person.givenNameDaniel
person.givenNameAna
person.givenNameAlexandra
person.givenNameMónica Alexandra
person.givenNamePedro
person.identifier.ciencia-id9A12-9450-7051
person.identifier.ciencia-idC212-F6D7-8240
person.identifier.ciencia-idD21D-88F0-DBD1
person.identifier.ciencia-idE015-7F8F-5CA1
person.identifier.orcid0000-0002-7307-4567
person.identifier.orcid0009-0001-9530-6349
person.identifier.orcid0000-0001-9410-4772
person.identifier.orcid0000-0003-2969-8177
person.identifier.orcid0000-0002-1206-1367
person.identifier.orcid0000-0002-3453-3978
person.identifier.scopus-author-id57194785077
person.identifier.scopus-author-id7004219471
relation.isAuthorOfPublication86dbddcb-a337-4d34-8e33-626c98b5b3b8
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