Evidence map›Paper›PMID 35859008›Full record

ArticleScientific reports2022

Cell-free DNA 5-hydroxymethylcytosine is an emerging marker of acute myeloid leukemia.

Jianming Shao, Sihan Wang, Diana West-Szymanski, Jason Karpus, Shilpan Shah, Siddhartha Ganguly, Janice Smith, Youli Zu, Chuan He, Zejuan Li

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Scientific reports, 2022. 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 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
4.5field-weighted citation impact, top 4% 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

19 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
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  6. Review
  7. Review
  8. Article
  9. A 5-Hydroxymethylcytosine-Based Noninvasive Model for Early Detection of Colorectal Carcinomas and Advanced Adenomas: The METHOD-2 Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Observational
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Epigenetic reprogramming in cancer: From diagnosis to treatment.Frontiers in cell and developmental biology · 2023
    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

10 authors at 5 institutions in 1 country.

Jianming ShaoDepartment of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA.
Sihan WangDepartment of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA.
Diana West-SzymanskiDepartment of Medicine, The University of Chicago, Chicago, IL, USA.
Jason KarpusDepartment of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, USA.
Shilpan ShahCancer Center, Houston Methodist Hospital, Houston, TX, USA.
Siddhartha GangulyCancer Center, Houston Methodist Hospital, Houston, TX, USA.
Janice SmithMolecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Youli ZuDepartment of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA.
Chuan HeDepartment of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, USA.
Zejuan LiDepartment of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA. zli3@houstonmethodist.org.
University of Chicago · USCornell University · USMethodist Hospital · USMethodist Hospital · USBaylor College of Medicine · US

Funding

Labeling and sequencing of 5hmC and 5mC in DNA-RenewalR01HG006827 · NHGRI · UNIVERSITY OF CHICAGO · PI HE, CHUAN · 2012 to 2025
$7.2M
Howard Hughes Medical InstituteNHGRI NIH HHS R01 HG006827
6 · The paper itself

Abstract

Aberrant changes in 5-hydroxymethylcytosine (5hmC) are a unique epigenetic feature in many cancers including acute myeloid leukemia (AML). However, genome-wide analysis of 5hmC in plasma cell-free DNA (cfDNA) remains unexploited in AML patients. We used a highly sensitive and robust nano-5hmC-Seal technology and profiled genome-wide 5hmC distribution in 239 plasma cfDNA samples from 103 AML patients and 81 non-cancer controls. We developed a 5hmC diagnostic model that precisely differentiates AML patients from controls with high sensitivity and specificity. We also developed a 5hmC prognostic model that accurately predicts prognosis in AML patients. High weighted prognostic scores (wp-scores) in AML patients were significantly associated with adverse overall survival (OS) in both training (P = 3.31e-05) and validation (P = 0.000464) sets. The wp-score was also significantly associated with genetic risk stratification and displayed dynamic changes with varied disease burden. Moreover, we found that high wp-scores in a single gene, BMS1 and GEMIN5 predicted OS in AML patients in both the training set (P = 0.023 and 0.031, respectively) and validation set (P = 9.66e-05 and 0.011, respectively). Lastly, our study demonstrated the genome-wide landscape of DNA hydroxymethylation in AML and revealed critical genes and pathways related to AML diagnosis and prognosis. Our data reveal plasma cfDNA 5hmC signatures as sensitive and accurate markers for AML diagnosis and prognosis. Plasma cfDNA 5hmC analysis will be an effective and minimally invasive tool for AML management.

Indexed as

Cell-Free Nucleic AcidsLeukemia, Myeloid, Acute5-MethylcytosineEpigenomicsHumans5-hydroxymethylcytosine5-MethylcytosineCell-Free Nucleic Acids

Identifiers

PMID35859008
PMCPMC9300744
OpenAlexW4286210026

What OpenQuestion holds

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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.