Evidence map›Paper›PMID 30616658›Full record

ArticleEpigenetics & chromatin2019

Global distribution of DNA hydroxymethylation and DNA methylation in chronic lymphocytic leukemia.

Sara Wernig-Zorc, Mukesh Pratap Yadav, Pradeep Kumar Kopparapu, Mats Bemark, Hallgerdur Lind Kristjansdottir, Per-Ola Andersson, Chandrasekhar Kanduri, Meena Kanduri

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Epigenetics & chromatin, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07060001 (Evaluation of the Efficacy of Hypomethylating Agent Versus Standard Intensive Chemotherapy Induction Based on 5hmC - a Novel, Blood Epigenetic Marker for Assessing Measurable Residual Disease in Patients With Acute Myeloid Leukemia), which is not on this map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.9field-weighted citation impact, top 26% 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.

NCT07060001 phase2not yet recruitingnot on this mapstarted 2026, after this paper: background citation

Evaluation of the Efficacy of Hypomethylating Agent Versus Standard Intensive Chemotherapy Induction Based on 5hmC - a Novel, Blood Epigenetic Marker for Assessing Measurable Residual Disease in Patients With Acute Myeloid Leukemia

TypeinterventionalSponsorThe Methodist Hospital Research InstituteRan2026 to 2029Enrolled112ConditionsAcute Myeloid Leukemia (AML), Acute Myeloid Leukaemia (AML)Arms5hmC Biomarker, Venetoclax, Decitabine 20 mg/m²/day for 5 days, Azacitidine (AZA), Cytarabine (Ara-C)
3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
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  10. Altered DNA Methylation Profiles inInternational journal of molecular sciences · 2021
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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

8 authors at 3 institutions in 1 country.

Sara Wernig-ZorcDepartment of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Mukesh Pratap YadavDepartment of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden.
Pradeep Kumar KopparapuDepartment of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden.
Mats BemarkDepartment of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Hallgerdur Lind KristjansdottirDepartment of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg University, Gothenburg, Sweden.
Per-Ola AnderssonDepartment of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg University, Gothenburg, Sweden.
Chandrasekhar KanduriDepartment of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Meena KanduriDepartment of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden. Meena.kanduri@gu.se.ORCID 0000-0003-2781-4779
University of Gothenburg · SESahlgrenska University Hospital · SESödra Älvsborg Hospital · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundChronic lymphocytic leukemia (CLL) has been a good model system to understand the functional role of 5-methylcytosine (5-mC) in cancer progression. More recently, an oxidized form of 5-mC, 5-hydroxymethylcytosine (5-hmC) has gained lot of attention as a regulatory epigenetic modification with prognostic and diagnostic implications for several cancers. However, there is no global study exploring the role of 5-hydroxymethylcytosine (5-hmC) levels in CLL. Herein, using mass spectrometry and hMeDIP-sequencing, we analysed the dynamics of 5-hmC during B cell maturation and CLL pathogenesis.

resultsWe show that naïve B-cells had higher levels of 5-hmC and 5-mC compared to non-class switched and class-switched memory B-cells. We found a significant decrease in global 5-mC levels in CLL patients (n = 15) compared to naïve and memory B cells, with no changes detected between the CLL prognostic groups. On the other hand, global 5-hmC levels of CLL patients were similar to memory B cells and reduced compared to naïve B cells. Interestingly, 5-hmC levels were increased at regulatory regions such as gene-body, CpG island shores and shelves and 5-hmC distribution over the gene-body positively correlated with degree of transcriptional activity. Importantly, CLL samples showed aberrant 5-hmC and 5-mC pattern over gene-body compared to well-defined patterns in normal B-cells. Integrated analysis of 5-hmC and RNA-sequencing from CLL datasets identified three novel oncogenic drivers that could have potential roles in CLL development and progression.

conclusionsThus, our study suggests that the global loss of 5-hmC, accompanied by its significant increase at the gene regulatory regions, constitute a novel hallmark of CLL pathogenesis. Our combined analysis of 5-mC and 5-hmC sequencing provided insights into the potential role of 5-hmC in modulating gene expression changes during CLL pathogenesis.

Indexed as

DNA Methylation5-MethylcytosineB-LymphocytesCase-Control StudiesCell Line, TumorHumansLeukemia, Lymphocytic, Chronic, B-Cell5-hydroxymethylcytosine5-MethylcytosineCpG islandsEnhancers and chronic lymphocytic leukemiaHydroxymethylation

Identifiers

PMID30616658
PMCPMC6322269
OpenAlexW2917109272

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.