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

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.

Základní údaje

Originální název

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

Autoři

SESTAKOVA, Sarka (203 Česká republika), Cyril SALEK (203 Česká republika), David KUNDRAT (203 Česká republika), Ela CEROVSKA (203 Česká republika), Jan VYDRA (203 Česká republika), Ivana JEŽÍŠKOVÁ (203 Česká republika, domácí), Adam FOLTA (203 Česká republika), Jiří MAYER (203 Česká republika, domácí), Petr CETKOVSKY (203 Česká republika) a Hana REMESOVA (203 Česká republika)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30205 Hematology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.700 v roce 2022

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1186/s13148-024-01625-x

UT WoS

001148303400001

Klíčová slova anglicky

Acute myeloid leukemia; DNA methylation; NGS; Prognosis

Štítky

14110212, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 21. 2. 2024 09:35, Mgr. Tereza Miškechová

Anotace

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.

Citovat

SESTAKOVA, Sarka, Cyril SALEK, David KUNDRAT, Ela CEROVSKA, Jan VYDRA, Ivana JEŽÍŠKOVÁ, Adam FOLTA, Jiří MAYER, Petr CETKOVSKY a Hana REMESOVA. MethScore as a new comprehensive DNA methylation-based value refining the prognosis in acute myeloid leukemia. CLINICAL EPIGENETICS. LONDON: BMC, 2024, roč. 16, č. 1, s. 1-12. ISSN 1868-7075. Dostupné z: https://dx.doi.org/10.1186/s13148-024-01625-x.

@article{2376682,
   author = {Sestakova, Sarka and Salek, Cyril and Kundrat, David and Cerovska, Ela and Vydra, Jan and Ježíšková, Ivana and Folta, Adam and Mayer, Jiří and Cetkovsky, Petr and Remesova, Hana},
   article_location = {LONDON},
   article_number = {1},
   doi = {http://dx.doi.org/10.1186/s13148-024-01625-x},
   keywords = {Acute myeloid leukemia; DNA methylation; NGS; Prognosis},
   language = {eng},
   issn = {1868-7075},
   journal = {CLINICAL EPIGENETICS},
   title = {MethScore as a new comprehensive DNA methylation-based value refining the prognosis in acute myeloid leukemia},
   url = {https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-024-01625-x},
   volume = {16},
   year = {2024}
}

TY  - JOUR
ID  - 2376682
AU  - Sestakova, Sarka - Salek, Cyril - Kundrat, David - Cerovska, Ela - Vydra, Jan - Ježíšková, Ivana - Folta, Adam - Mayer, Jiří - Cetkovsky, Petr - Remesova, Hana
PY  - 2024
TI  - MethScore as a new comprehensive DNA methylation-based value refining the prognosis in acute myeloid leukemia
JF  - CLINICAL EPIGENETICS
VL  - 16
IS  - 1
SP  - 1-12
EP  - 1-12
PB  - BMC
SN  - 18687075
KW  - Acute myeloid leukemia
KW  - DNA methylation
KW  - NGS
KW  - Prognosis
UR  - https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-024-01625-x
N2  - 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.
ER  -

SESTAKOVA, Sarka, Cyril SALEK, David KUNDRAT, Ela CEROVSKA, Jan VYDRA, Ivana JEŽÍŠKOVÁ, Adam FOLTA, Jiří MAYER, Petr CETKOVSKY a Hana REMESOVA. MethScore as a new comprehensive DNA methylation-based value refining the prognosis in acute myeloid leukemia. \textit{CLINICAL EPIGENETICS}. LONDON: BMC, 2024, roč.~16, č.~1, s.~1-12. ISSN~1868-7075. Dostupné z: https://dx.doi.org/10.1186/s13148-024-01625-x.

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