Evidence map›Paper›PMID 41044657›Full record

ArticleClinical epigenetics2025

Epigenetic risk stratification in juvenile myelomonocytic leukemia by targeted methylation analysis of the BMP4 locus.

Foued Ghanjati, Annika Heck, Dirk Lebrecht, Peter Nöllke, Felicia Andresen, Natalia Rotari, Marlou Schoof, Maximilian Schönung, Daniel B Lipka, Michael Dworzak and 15 more

Abstract read
In one paragraph

Article in Clinical epigenetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

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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

25 authors.

Foued GhanjatiDepartment of Pediatric Hematology and Oncology, Children's Hospital, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany. foued.ghanjati@uniklinik-freiburg.de.
Annika HeckDepartment of Pediatric Hematology and Oncology, Children's Hospital, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Dirk LebrechtDepartment of Pediatric Hematology and Oncology, Children's Hospital, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Peter NöllkeDepartment of Pediatric Hematology and Oncology, Children's Hospital, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Felicia AndresenDepartment of Pediatric Hematology and Oncology, Children's Hospital, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Natalia RotariDepartment of Pediatric Hematology and Oncology, Children's Hospital, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Marlou SchoofDepartment of Pediatric Hematology and Oncology, Children's Hospital, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Maximilian SchönungSection of Translational Cancer Epigenomics, Division of Translational Medical Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Daniel B LipkaSection of Translational Cancer Epigenomics, Division of Translational Medical Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Michael DworzakSt. Anna Children's Hospital, Department of Pediatrics and Adolescent Medicine, Anna Children's Cancer Research Institute (CCRI), Medical University of Vienna, and St., Vienna, Austria.
Barbara De MoerlooseDepartment of Paediatric Haematology-Oncology, Ghent University Hospital, Ghent, Belgium.
Martina SukovaDepartment of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
Henrik HasleDepartment of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.
Kirsi JahnukainenDivision of Hematology-Oncology and SCT Children´S Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Andrea MalonePediatric Haematology, Our Lady's Children's Hospital, Dublin, Ireland.
Riccardo MasettiPediatric Oncology and Haematology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy.
Jochen BuechnerDepartment of Pediatric Hematology and Oncology, Oslo University Hospital, Oslo, Norway.
Marek UssowiczDepartment of Pediatric Hematology and Oncology, BMT Unit CIC 817, Wroclaw Medical University, Wrocław, Poland.
Albert CatalaDepartment of Hematology and Oncology, Hospital Sant Joan de Deu, Barcelona, Spain.
Dominik TurkiewiczDepartment of Pediatrics, Section of Pediatric Oncology, Hematology, Immunology and Nephrology, Skåne University Hospital, Lund, Sweden.
Valérie de HaasDutch Childhood Oncology Group, Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands.
Markus SchmuggeDepartment of Hematology and Oncology, University Children's Hospital, Zurich, Switzerland.
Miriam ErlacherDepartment of Pediatric Hematology and Oncology, Children's Hospital, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Charlotte M NiemeyerDepartment of Pediatric Hematology and Oncology, Children's Hospital, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Christian FlothoDepartment of Pediatric Hematology and Oncology, Children's Hospital, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany. christian.flotho@uniklinik-freiburg.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Juvenile myelomonocytic leukemia (JMML) is a rare pediatric myelodysplastic/myeloproliferative neoplasm characterized by distinct epigenetic signatures that facilitate molecular classification. This study aimed to evaluate the diagnostic utility of locus-specific DNA methylation in the bone morphogenetic protein 4 (BMP4) gene as a single predictor of disease outcomes in a cohort of 111 children diagnosed with JMML, alongside 9 healthy controls. Methylation levels of BMP4, assessed through targeted bisulfite next-generation sequencing (bs-NGS), were heterogeneous within the JMML cohort and were significantly associated with clinical risk factors, such as patient age, and fetal hemoglobin (HbF) levels. A comparative analysis of BMP4 bs-NGS and genome-wide methylation array data revealed a strong positive correlation (p < 0.001). The sensitivity and specificity of BMP4 bs-NGS for classifying high-methylation cases were 0.612 and 0.887, respectively. For PTPN11-mutant patients (N = 40), the sensitivity was 0.667 and the specificity was 0.842. Survival analysis indicated that patients with high BMP4 methylation (BMP4h) had lower 5-year disease-free survival (DFS) rates than those with normal BMP4 methylation (BMP4n). Specifically, the 20% of patients with highest BMP4 methylation had a 5-year DFS of 0.38, in contrast to 0.62 for the lowest 20% (p = 0.007). These findings highlight the potential of BMP4 methylation analysis as a complementary biomarker for JMML risk stratification, mirroring genome-wide methylation profiles known to associate with prognostic subgroups.

Indexed as

Bone Morphogenetic Protein 4DNA MethylationLeukemia, Myelomonocytic, JuvenileAdolescentCase-Control StudiesChildChild, PreschoolEpigenesis, GeneticFemaleHigh-Throughput Nucleotide SequencingHumansInfantMalePrognosisProtein Tyrosine Phosphatase, Non-Receptor Type 11Risk AssessmentBMP4 protein, humanBone Morphogenetic Protein 4Protein Tyrosine Phosphatase, Non-Receptor Type 11PTPN11 protein, humanAbstract word count = 217BiomarkerBMP4Bs-NGSDNA methylationJMMLRisk stratificationText word count = 3077

Identifiers

PMID41044657
PMCPMC12492826

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