Evidence map›Paper›PMID 37060567›Full record

ArticleCell reports2023

Elevated enhancer-oncogene contacts and higher oncogene expression levels by recurrent CTCF inactivating mutations in acute T cell leukemia.

Willem K Smits, Carlo Vermeulen, Rico Hagelaar, Shunsuke Kimura, Eric M Vroegindeweij, Jessica G C A M Buijs-Gladdines, Ellen van de Geer, Marjon J A M Verstegen, Erik Splinter, Simon V van Reijmersdal and 9 more

Abstract read
In one paragraph

Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Oncogenic Enhancers in Leukemia.Blood cancer discovery · 2024
    Review
  4. Review
  5. Review
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

19 authors.

Willem K SmitsPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Carlo VermeulenOncode Institute, Utrecht, the Netherlands; Hubrecht Institute-KNAW, Utrecht, the Netherlands; Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
Rico HagelaarPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Oncode Institute, Utrecht, the Netherlands.
Shunsuke KimuraLaboratory of Pathology, St. Jude's Children's Research Hospital, Memphis TN, USA.
Eric M VroegindeweijPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Jessica G C A M Buijs-GladdinesPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Ellen van de GeerPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Marjon J A M VerstegenOncode Institute, Utrecht, the Netherlands; Hubrecht Institute-KNAW, Utrecht, the Netherlands.
Erik SplinterCergentis BV, Utrecht, the Netherlands.
Simon V van ReijmersdalPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Arjan BuijsDepartment of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
Niels GaljartDepartment of Cell Biology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.
Winfried van EyndhovenDiagnostics and Genomics Group, Agilent Technologies, Amstelveen, the Netherlands.
Max van MinCergentis BV, Utrecht, the Netherlands.
Roland KuiperPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Department of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
Patrick KemmerenPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Charles G MullighanLaboratory of Pathology, St. Jude's Children's Research Hospital, Memphis TN, USA.
Wouter de LaatOncode Institute, Utrecht, the Netherlands; Hubrecht Institute-KNAW, Utrecht, the Netherlands.
Jules P P MeijerinkPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands. Electronic address: jules.meijerink@acerta-pharma.com.

Funding

Translating genomic discoveries to improved outcomes for high risk acute leukemiaR35CA197695 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Charles G Mullighan · 2017 to 2026
$11.4M
NCI NIH HHS R35 CA197695
6 · The paper itself

Abstract

Monoallelic inactivation of CCCTC-binding factor (CTCF) in human cancer drives altered methylated genomic states, altered CTCF occupancy at promoter and enhancer regions, and deregulated global gene expression. In patients with T cell acute lymphoblastic leukemia (T-ALL), we find that acquired monoallelic CTCF-inactivating events drive subtle and local genomic effects in nearly half of t(5; 14) (q35; q32.2) rearranged patients, especially when CTCF-binding sites are preserved in between the BCL11B enhancer and the TLX3 oncogene. These solitary intervening sites insulate TLX3 from the enhancer by inducing competitive looping to multiple binding sites near the TLX3 promoter. Reduced CTCF levels or deletion of the intervening CTCF site abrogates enhancer insulation by weakening competitive looping while favoring TLX3 promoter to BCL11B enhancer looping, which elevates oncogene expression levels and leukemia burden.

Indexed as

Precursor T-Cell Lymphoblastic Leukemia-LymphomaCCCTC-Binding FactorChromatinEnhancer Elements, GeneticHumansMutationOncogenesRepressor ProteinsTranscription FactorsTumor Suppressor ProteinsBCL11B protein, humanCCCTC-Binding FactorChromatinCTCF protein, humanRepressor ProteinsTranscription FactorsTumor Suppressor ProteinsBCL11Bcompetitive chromatin loopingCP: CancerCTCF mutationenhancer insulationoncogene regulationT cell acute lymphoblastic leukemiaTLX3

Identifiers

PMID37060567
PMCPMC10750298

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.