Publication details

MethScore as a new comprehensive DNA methylation-based value refining the prognosis in acute myeloid leukemia

Authors

SESTAKOVA Sarka SALEK Cyril KUNDRAT David CEROVSKA Ela VYDRA Jan JEŽÍŠKOVÁ Ivana FOLTA Adam MAYER Jiří CETKOVSKY Petr REMESOVA Hana

Year of publication 2024
Type Article in Periodical
Magazine / Source CLINICAL EPIGENETICS
MU Faculty or unit

Faculty of Medicine

Citation
Web https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-024-01625-x
Doi http://dx.doi.org/10.1186/s13148-024-01625-x
Keywords Acute myeloid leukemia; DNA methylation; NGS; Prognosis
Description Background Changes in DNA methylation are common events in the pathogenesis of acute myeloid leukemia (AML) and have been repeatedly reported as associated with prognosis. However, studies integrating these numerous and potentially prognostically relevant DNA methylation changes are lacking. Therefore, we aimed for an overall evaluation of these epigenetic aberrations to provide a comprehensive NGS-based approach of DNA methylation assessment for AML prognostication.Results We designed a sequencing panel targeting 239 regions (approx. 573 kb of total size) described in the literature as having a prognostic impact or being associated with AML pathogenesis. Diagnostic whole-blood DNA samples of adult AML patients divided into a training (n = 128) and a testing cohort (n = 50) were examined. The libraries were prepared using SeqCap Epi Enrichments System (Roche) and sequenced on MiSeq instrument (Illumina). Altogether, 1935 CpGs affecting the survival (p < 0.05) were revealed in the training cohort. A summarizing value MethScore was then calculated from these significant CpGs. Patients with lower MethScore had markedly longer overall survival (OS) and event-free survival (EFS) than those with higher MethScore (p < 0.001). The predictive ability of MethScore was verified on the independent testing cohort for OS (p = 0.01). Moreover, the proof-of-principle validation was performed using the TCGA dataset.Conclusions We showed that comprehensive NGS-based approach of DNA methylation assessment revealed a robust epigenetic signature relevant to AML outcome. We called this signature MethScore and showed it might serve as a strong prognostic marker able to refine survival probability of AML patients.

You are running an old browser version. We recommend updating your browser to its latest version.

More info