Evidence map›Paper›PMID 25266220›Full record

ArticleJournal of hematology & oncology2014

CBFB-MYH11 hypomethylation signature and PBX3 differential methylation revealed by targeted bisulfite sequencing in patients with acute myeloid leukemia.

Hana Hájková, Markus Hsi-Yang Fritz, Cedrik Haškovec, Jiří Schwarz, Cyril Šálek, Jana Marková, Zdeněk Krejčík, Michaela Dostálová Merkerová, Arnošt Kostečka, Martin Vostrý and 4 more

Open access · goldAbstract read
In one paragraph

Article in Journal of hematology & oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.2field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. PBX3 in Cancer.Cancers · 2020
    Review
  5. Review
  6. Review
  7. Article
  8. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 2 countries.

Hana Hájková
Markus Hsi-Yang Fritz
Cedrik Haškovec
Jiří Schwarz
Cyril Šálek
Jana Marková
Zdeněk Krejčík
Michaela Dostálová Merkerová
Arnošt Kostečka
Martin Vostrý
Ota Fuchs
Kyra Michalová
Petr Cetkovský
Vladimír Beneš
Institute of Haematology and Blood Transfusion · CZEuropean Molecular Biology Laboratory · DECharles University · CZ

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundStudying DNA methylation changes in the context of structural rearrangements and point mutations as well as gene expression changes enables the identification of genes that are important for disease onset and progression in different subtypes of acute myeloid leukemia (AML) patients. The aim of this study was to identify differentially methylated genes with potential impact on AML pathogenesis based on the correlation of methylation and expression data.

methodsThe primary method of studying DNA methylation changes was targeted bisulfite sequencing capturing approximately 84 megabases (Mb) of the genome in 14 diagnostic AML patients and a healthy donors' CD34+ pool. Subsequently, selected DNA methylation changes were confirmed by 454 bisulfite pyrosequencing in a larger cohort of samples. Furthermore, we addressed gene expression by microarray profiling and correlated methylation of regions adjacent to transcription start sites with expression of corresponding genes.

resultsHere, we report a novel hypomethylation pattern, specific to CBFB-MYH11 fusion resulting from inv(16) rearrangement that is associated with genes previously described as upregulated in inv(16) AML. We assume that this hypomethylation and corresponding overexpresion occurs in the genes whose function is important in inv(16) leukemogenesis. Further, by comparing all targeted methylation and microarray expression data, PBX3 differential methylation was found to correlate with its gene expression. PBX3 has been recently shown to be a key interaction partner of HOX genes during leukemogenesis and we revealed higher incidence of relapses in PBX3-overexpressing patients.

conclusionsWe discovered new genomic regions with aberrant DNA methylation that are associated with expression of genes involved in leukemogenesis. Our results demonstrate the potential of the targeted approach for DNA methylation studies to reveal new regulatory regions.

Indexed as

Biomarkers, TumorCluster AnalysisDNA MethylationFemaleGene Expression Regulation, LeukemicHomeodomain ProteinsHumansKaplan-Meier EstimateLeukemia, Myeloid, AcuteMaleOncogene Proteins, FusionPrognosisProportional Hazards ModelsProto-Oncogene ProteinsReal-Time Polymerase Chain ReactionTranscriptomeBiomarkers, TumorCBFbeta-MYH11 fusion proteinHomeodomain ProteinsOncogene Proteins, Fusionproto-oncogene protein Pbx3Proto-Oncogene Proteins

Identifiers

PMID25266220
PMCPMC4197269
OpenAlexW2277667612

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.