Evidence map›Paper›PMID 39443995›Full record

ArticleMolecular cancer2024

Epigenome-wide analysis across the development span of pediatric acute lymphoblastic leukemia: backtracking to birth.

Akram Ghantous, Semira Gonseth Nusslé, Farah J Nassar, Natalia Spitz, Alexei Novoloaca, Olga Krali, Eric Nickels, Vincent Cahais, Cyrille Cuenin, Ritu Roy and 21 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Age-Driven Genetic and Epigenetic Heterogeneity in B-ALL.International journal of molecular sciences · 2025
    Review
  8. Review
  9. Article
  10. Article
  11. The DNA methylation landscape of musculoskeletal sarcomas.Exploration of targeted anti-tumor therapy · 2025
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

31 authors.

Akram Ghantous *Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, (IARC), 25 avenue Tony Garnier, CS 90627, Lyon, Cedex 07 69366, France. GhantousA@iarc.who.int.
Semira Gonseth Nusslé *Genknowme SA, Alanine Building, Corniche Road 5, 1066, Epalinges, Switzerland.
Farah J Nassar *Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, (IARC), 25 avenue Tony Garnier, CS 90627, Lyon, Cedex 07 69366, France.
Natalia SpitzEpigenomics and Mechanisms Branch, International Agency for Research on Cancer, (IARC), 25 avenue Tony Garnier, CS 90627, Lyon, Cedex 07 69366, France.
Alexei NovoloacaEpigenomics and Mechanisms Branch, International Agency for Research on Cancer, (IARC), 25 avenue Tony Garnier, CS 90627, Lyon, Cedex 07 69366, France.
Olga KraliDepartment of Medical Sciences, Molecular Precision Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Eric NickelsCenter for Genetic Epidemiology, University of Southern California, Los Angeles, USA.
Vincent CahaisEpigenomics and Mechanisms Branch, International Agency for Research on Cancer, (IARC), 25 avenue Tony Garnier, CS 90627, Lyon, Cedex 07 69366, France.
Cyrille CueninEpigenomics and Mechanisms Branch, International Agency for Research on Cancer, (IARC), 25 avenue Tony Garnier, CS 90627, Lyon, Cedex 07 69366, France.
Ritu RoyComputational Biology and Informatics Core, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, USA.
Shaobo LiCenter for Genetic Epidemiology, University of Southern California, Los Angeles, USA.
Maxime CaronDepartment of Pediatrics, University of Montreal & Research Center, Centre Hospitalier Universitaire (CHU) Sainte-Justine, Montréal, Quebec, Canada.
Dilys LamSchool of Molecular Sciences, The University of Western Australia, Crawley, Western Australia, 6009, Australia.
Peter Daniel FransquetCentre for Social and Early Emotional Development (SEED), School of Psychology, Deakin University, Burwood, Victoria, Australia.
John CasementBioinformatics Support Unit, Newcastle University, Newcastle upon Tyne, UK.
Gordon StrathdeeNewcastle University Centre for Cancer, Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Mark S PearcePopulation Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Helen M HansenNeuro and Molecular Epidemiology Laboratory, University of California San Francisco, San Francisco, USA.
Hwi-Ho LeeDepartment of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, 10408, Korea.
Yong Sun LeeDepartment of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, 10408, Korea.
Adam J de SmithCenter for Genetic Epidemiology, University of Southern California, Los Angeles, USA.
Daniel SinnettDepartment of Pediatrics, University of Montreal & Research Center, Centre Hospitalier Universitaire (CHU) Sainte-Justine, Montréal, Quebec, Canada.
Siri Eldevik HåbergCentre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
Jill A McKayDepartment of Applied Sciences, Northumbria University, Newcastle upon Tyne, UK.
Jessica NordlundDepartment of Medical Sciences, Molecular Precision Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Per MagnusCentre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
Terence DwyerClinical Sciences Theme, Heart Group, Murdoch Children's Research Institute, Melbourne, Australia.
Richard SafferyMurdoch Children's Research Institute and Department of Paediatrics, University of Melbourne, Melbourne, Australia.
Joseph Leo Wiemels *Center for Genetic Epidemiology, University of Southern California, Los Angeles, USA.
Monica Cheng Munthe-Kaas *Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
Zdenko Herceg *Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, (IARC), 25 avenue Tony Garnier, CS 90627, Lyon, Cedex 07 69366, France. HercegZ@iarc.who.int.

Funding

Environmental and Molecular Epidemiology of Childhood LeukemiaR01ES009137 · NIEHS · UNIVERSITY OF CALIFORNIA BERKELEY · PI METAYER, CATHERINE · 1999 to 2013
$21.1M
Project 3: Prenatal Exposure, DNA Methylation & Childhood LeukemiaP01ES018172 · NIEHS · UNIVERSITY OF CALIFORNIA BERKELEY · PI METAYER, CATHERINE · 2009 to 2013
$3.7M
Perinatal immune development and risk of childhood acute lymphoblastic leukemiaR01CA175737 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MA, XIAOMEI, WIEMELS, JOSEPH LEO · 2014 to 2018
$3.0M
NCI NIH HHS R01 CA175737NIEHS NIH HHS P01 ES018172NIEHS NIH HHS R01 ES009137World Health Organization 001
6 · The paper itself

Abstract

backgroundCancer is the leading cause of disease-related mortality in children. Causes of leukemia, the most common form, are largely unknown. Growing evidence points to an origin in-utero, when global redistribution of DNA methylation occurs driving tissue differentiation.

methodsEpigenome-wide DNA methylation was profiled in surrogate (blood) and target (bone marrow) tissues at birth, diagnosis, remission and relapse of pediatric pre-B acute lymphoblastic leukemia (pre-B ALL) patients. Double-blinded analyses was performed between prospective cohorts extending from birth to diagnosis and retrospective studies backtracking from clinical disease to birth. Validation was carried out using independent technologies and populations.

resultsThe imprinted and immuno-modulating VTRNA2-1 was hypermethylated (FDR<0.05) at birth in nested cases relative to controls in all tested populations (totaling 317 cases and 483 controls), including European and Hispanic ancestries. VTRNA2-1 methylation was stable over follow-up years after birth and across surrogate, target and other tissues (n=5,023 tissues; 30 types). When profiled in leukemic tissues from two clinical cohorts (totaling 644 cases), VTRNA2-1 methylation exhibited higher levels at diagnosis relative to controls, it reset back to normal levels at remission, and then re-increased to above control levels at relapse. Hypermethylation was significantly associated with worse pre-B ALL patient survival and with reduced VTRNA2-1 expression (n=2,294 tissues; 26 types), supporting a functional and translational role for VTRNA2-1 methylation.

conclusionThis study provides proof-of-concept to detect at birth epigenetic precursors of pediatric pre-B ALL. These alterations were reproducible with different technologies, in three continents and in two ethnicities, and can offer biomarkers for early detection and prognosis as well as actionable targets for therapy.

Indexed as

DNA MethylationEpigenesis, GeneticEpigenomePrecursor Cell Lymphoblastic Leukemia-LymphomaAdolescentBiomarkers, TumorCase-Control StudiesChildChild, PreschoolFemaleHumansInfantInfant, NewbornMalePrognosisBiomarkers, TumorBirth cohortDNA methylationEpigeneticsNeonatal blood spotsPediatric leukemiaVTRNA2-1

Identifiers

PMID39443995
PMCPMC11515509

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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.