DNA methylation and hydroxymethylation patterns in acute
myeloid leukemia patients with mutations in DNMT3A and IDH1/2
and their combinations

J 2019

DNA methylation and hydroxymethylation patterns in acute myeloid leukemia patients with mutations in DNMT3A and IDH1/2 and their combinations

ŠESTÁKOVÁ, Šárka, Zdeněk KREJČÍK, Adam FOLTA, Eva CEROVSKÁ, Cyril ŠÁLEK et. al.

Basic information

Original name

DNA methylation and hydroxymethylation patterns in acute myeloid leukemia patients with mutations in DNMT3A and IDH1/2 and their combinations

Authors

ŠESTÁKOVÁ, Šárka (203 Czech Republic), Zdeněk KREJČÍK (203 Czech Republic), Adam FOLTA (203 Czech Republic), Eva CEROVSKÁ (203 Czech Republic), Cyril ŠÁLEK (203 Czech Republic), Michaela MERKEROVÁ DOSTÁLOVÁ (203 Czech Republic), Pavla PECHERKOVÁ (203 Czech Republic), Zdeněk RÁČIL (203 Czech Republic, belonging to the institution), Jiří MAYER (203 Czech Republic, belonging to the institution), Petr CETKOVSKÝ (203 Czech Republic) and Hana REMEŠOVÁ (203 Czech Republic, guarantor)

Edition

Cancer Biomarkers, Amsterdam, IOS Press, 2019, 1574-0153

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 3.436

RIV identification code

RIV/00216224:14110/19:00108493

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.3233/CBM-182176

UT WoS

000469000100005

Keywords in English

AML; DNMT3A and IDH1/2 mutations; methylation; hydroxymethylation; GZMB; CHFR

Abstract

V originále

BACKGROUND: Aberrant epigenetic patterns are a hallmark of acute myeloid leukemia (AML). Mutations in profound epigenetic regulators DNMT3A and IDH1/2 often occur concurrently in AML. OBJECTIVES: The aim was to analyze DNA methylation, hydroxymethylation and mRNA expression profiles in AML with mutations in DNMT3A and IDH1/2 (individually and in combinations). METHODS: Infinium MethylationEPIC BeadChip (Illumina) covering 850,000 CpGs was utilized. The validation of hydroxy-/methylation data was done by pyrosequencing. HumanHT-12 v4 Expression BeadChip (Illumina) was used for expression examination. RESULTS: Hierarchical clustering analysis of DNA hydroxy-/methylation data revealed clusters corresponding to DNMT3A and IDH1/2 mutations and CD34+ healthy controls. Samples with concurrent presence of DNMT3A and IDH1/2 mutations displayed mixed DNA hydroxy-/methylation profile with preferential clustering to healthy controls. Numbers and levels of DNA hydroxymethylation were low. Uniformly hypermethylated loci in AML patients with IDH1/2 mutations were enriched for immune response and apoptosis related genes, among which hypermethylation of granzyme B (GZMB) was found to be associated with inferior overall survival of AML patients (P = 0.035). CONCLUSIONS: Distinct molecular background results in specific DNA hydroxy-/methylation profiles in AML. Site-specific DNA hydroxymethylation changes are much less frequent in AML pathogenesis compared to DNA methylation. Methylation levels of enhancer located upstream GZMB gene might contribute to AML prognostication models.

Links

NV15-25809A, research and development project

Name: Národní program studia mutací a klonality leukemických buněk u pacientů s akutní myeloidní leukémií

Citovat

ŠESTÁKOVÁ, Šárka, Zdeněk KREJČÍK, Adam FOLTA, Eva CEROVSKÁ, Cyril ŠÁLEK, Michaela MERKEROVÁ DOSTÁLOVÁ, Pavla PECHERKOVÁ, Zdeněk RÁČIL, Jiří MAYER, Petr CETKOVSKÝ and Hana REMEŠOVÁ. DNA methylation and hydroxymethylation patterns in acute myeloid leukemia patients with mutations in DNMT3A and IDH1/2 and their combinations. Cancer Biomarkers. Amsterdam: IOS Press, 2019, vol. 25, No 1, p. 43-51. ISSN 1574-0153. Available from: https://dx.doi.org/10.3233/CBM-182176.

@article{1545957,
   author = {Šestáková, Šárka and Krejčík, Zdeněk and Folta, Adam and Cerovská, Eva and Šálek, Cyril and Merkerová Dostálová, Michaela and Pecherková, Pavla and Ráčil, Zdeněk and Mayer, Jiří and Cetkovský, Petr and Remešová, Hana},
   article_location = {Amsterdam},
   article_number = {1},
   doi = {http://dx.doi.org/10.3233/CBM-182176},
   keywords = {AML; DNMT3A and IDH1/2 mutations; methylation; hydroxymethylation; GZMB; CHFR},
   language = {eng},
   issn = {1574-0153},
   journal = {Cancer Biomarkers},
   title = {DNA methylation and hydroxymethylation patterns in acute myeloid leukemia patients with mutations in DNMT3A and IDH1/2 and their combinations},
   url = {http://dx.doi.org/10.3233/CBM-182176},
   volume = {25},
   year = {2019}
}

TY  - JOUR
ID  - 1545957
AU  - Šestáková, Šárka - Krejčík, Zdeněk - Folta, Adam - Cerovská, Eva - Šálek, Cyril - Merkerová Dostálová, Michaela - Pecherková, Pavla - Ráčil, Zdeněk - Mayer, Jiří - Cetkovský, Petr - Remešová, Hana
PY  - 2019
TI  - DNA methylation and hydroxymethylation patterns in acute myeloid leukemia patients with mutations in DNMT3A and IDH1/2 and their combinations
JF  - Cancer Biomarkers
VL  - 25
IS  - 1
SP  - 43-51
EP  - 43-51
PB  - IOS Press
SN  - 15740153
KW  - AML
KW  - DNMT3A and IDH1/2 mutations
KW  - methylation
KW  - hydroxymethylation
KW  - GZMB
KW  - CHFR
UR  - http://dx.doi.org/10.3233/CBM-182176
L2  - http://dx.doi.org/10.3233/CBM-182176
N2  - BACKGROUND: Aberrant epigenetic patterns are a hallmark of acute myeloid leukemia (AML). Mutations in profound epigenetic regulators DNMT3A and IDH1/2 often occur concurrently in AML. OBJECTIVES: The aim was to analyze DNA methylation, hydroxymethylation and mRNA expression profiles in AML with mutations in DNMT3A and IDH1/2 (individually and in combinations). METHODS: Infinium MethylationEPIC BeadChip (Illumina) covering 850,000 CpGs was utilized. The validation of hydroxy-/methylation data was done by pyrosequencing. HumanHT-12 v4 Expression BeadChip (Illumina) was used for expression examination. RESULTS: Hierarchical clustering analysis of DNA hydroxy-/methylation data revealed clusters corresponding to DNMT3A and IDH1/2 mutations and CD34+ healthy controls. Samples with concurrent presence of DNMT3A and IDH1/2 mutations displayed mixed DNA hydroxy-/methylation profile with preferential clustering to healthy controls. Numbers and levels of DNA hydroxymethylation were low. Uniformly hypermethylated loci in AML patients with IDH1/2 mutations were enriched for immune response and apoptosis related genes, among which hypermethylation of granzyme B (GZMB) was found to be associated with inferior overall survival of AML patients (P = 0.035). CONCLUSIONS: Distinct molecular background results in specific DNA hydroxy-/methylation profiles in AML. Site-specific DNA hydroxymethylation changes are much less frequent in AML pathogenesis compared to DNA methylation. Methylation levels of enhancer located upstream GZMB gene might contribute to AML prognostication models.
ER  -

ŠESTÁKOVÁ, Šárka, Zdeněk KREJČÍK, Adam FOLTA, Eva CEROVSKÁ, Cyril ŠÁLEK, Michaela MERKEROVÁ DOSTÁLOVÁ, Pavla PECHERKOVÁ, Zdeněk RÁČIL, Jiří MAYER, Petr CETKOVSKÝ and Hana REMEŠOVÁ. DNA methylation and hydroxymethylation patterns in acute myeloid leukemia patients with mutations in DNMT3A and IDH1/2 and their combinations. \textit{Cancer Biomarkers}. Amsterdam: IOS Press, 2019, vol.~25, No~1, p.~43-51. ISSN~1574-0153. Available from: https://dx.doi.org/10.3233/CBM-182176.

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