J 2024

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

SESTAKOVA, Sarka, Cyril SALEK, David KUNDRAT, Ela CEROVSKA, Jan VYDRA et. al.

Basic information

Original name

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

Authors

SESTAKOVA, Sarka (203 Czech Republic), Cyril SALEK (203 Czech Republic), David KUNDRAT (203 Czech Republic), Ela CEROVSKA (203 Czech Republic), Jan VYDRA (203 Czech Republic), Ivana JEŽÍŠKOVÁ (203 Czech Republic, belonging to the institution), Adam FOLTA (203 Czech Republic), Jiří MAYER (203 Czech Republic, belonging to the institution), Petr CETKOVSKY (203 Czech Republic) and Hana REMESOVA (203 Czech Republic)

Edition

CLINICAL EPIGENETICS, LONDON, BMC, 2024, 1868-7075

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 5.700 in 2022

Organization unit

Faculty of Medicine

DOI

UT WoS

001148303400001

Keywords in English

Acute myeloid leukemia; DNA methylation; NGS; Prognosis

Tags

Tags

International impact, Reviewed
Změněno: 21/2/2024 09:35, Mgr. Tereza Miškechová

Abstract

V originále

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.