Evidence map›Paper›PMID 22922567›Full record

ArticleLeukemia2013

450K-array analysis of chronic lymphocytic leukemia cells reveals global DNA methylation to be relatively stable over time and similar in resting and proliferative compartments.

N Cahill, A-C Bergh, M Kanduri, H Göransson-Kultima, L Mansouri, A Isaksson, F Ryan, K E Smedby, G Juliusson, C Sundström and 2 more

Abstract readComparative Study
PubMed Publisher
In one paragraph

Article in Leukemia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

60 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. Altered DNA Methylation Profiles inInternational journal of molecular sciences · 2021
    Article
  11. Article
  12. Future science OA · 2020
    Article
  13. Article
  14. Article
  15. Article
  16. Clonal dynamics in chronic lymphocytic leukemia.Hematology. American Society of Hematology. Education Program · 2019
    Review
  17. Article
  18. Article
  19. Article
  20. Article
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

12 authors.

N CahillDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
A-C Bergh
M Kanduri
H Göransson-Kultima
L Mansouri
A Isaksson
F Ryan
K E Smedby
G Juliusson
C Sundström
A Rosén
R Rosenquist

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In chronic lymphocytic leukemia (CLL), the microenvironment influences gene expression patterns; however, knowledge is limited regarding the extent to which methylation changes with time and exposure to specific microenvironments. Using high-resolution 450K arrays, we provide the most comprehensive DNA methylation study of CLL to date, analyzing paired diagnostic/follow-up samples from IGHV-mutated/untreated and IGHV-unmutated/treated patients (n=36) and patient-matched peripheral blood and lymph node samples (n=20). On an unprecedented scale, we revealed 2239 differentially methylated CpG sites between IGHV-mutated and unmutated patients, with the majority of sites positioned outside annotated CpG islands. Intriguingly, CLL prognostic genes (for example, CLLU1, LPL, ZAP70 and NOTCH1), epigenetic regulator (for example, HDAC9, HDAC4 and DNMT3B), B-cell signaling (for example, IBTK) and numerous TGF-β and NF-κB/TNF pathway genes were alternatively methylated between subgroups. Contrary, DNA methylation over time was deemed rather stable with few recurrent changes noted within subgroups. Although a larger number of non-recurrent changes were identified among IGHV-unmutated relative to mutated cases over time, these equated to a low global change. Similarly, few changes were identified between compartment cases. Altogether, we reveal CLL subgroups to display unique methylation profiles and unveil methylation as relatively stable over time and similar within different CLL compartments, implying aberrant methylation as an early leukemogenic event.

Indexed as

Cell ProliferationDNA MethylationGene Expression ProfilingAgedBiomarkers, TumorB-LymphocytesCase-Control StudiesCohort StudiesCpG IslandsDisease ProgressionDNA, NeoplasmFemaleGenome-Wide Association StudyHumansImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionBiomarkers, TumorDNA, NeoplasmImmunoglobulin Heavy ChainsImmunoglobulin Variable Region

Identifiers

PMID22922567

What OpenQuestion holds

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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.