Journal Article

DKFZ-2025-02035

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Epigenetic risk stratification in juvenile myelomonocytic leukemia by targeted methylation analysis of the BMP4 locus.

Ghanjati, F. ; Heck, A. ; Lebrecht, D. ; Nöllke, P. ; Andresen, F. ; Rotari, N. ; Schoof, M. ; Schönung, M.DKFZ* ; Lipka, D. B.DKFZ* ; Dworzak, M. ; De Moerloose, B. ; Sukova, M. ; Hasle, H. ; Jahnukainen, K. ; Malone, A. ; Masetti, R. ; Buechner, J. ; Ussowicz, M. ; Catala, A. ; Turkiewicz, D. ; de Haas, V. ; Schmugge, M. ; Erlacher, M.DKFZ* ; Niemeyer, C. M.DKFZ* ; Flotho, C.DKFZ*

2025
BioMed Central [Erscheinungsort nicht ermittelbar]

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Please use a persistent id in citations: doi:10.1186/s13148-025-01983-0

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.

Keyword(s): Humans (MeSH) ; DNA Methylation (MeSH) ; Bone Morphogenetic Protein 4: genetics (MeSH) ; Leukemia, Myelomonocytic, Juvenile: genetics (MeSH) ; Leukemia, Myelomonocytic, Juvenile: diagnosis (MeSH) ; Male (MeSH) ; Female (MeSH) ; Epigenesis, Genetic (MeSH) ; Child (MeSH) ; Child, Preschool (MeSH) ; Infant (MeSH) ; High-Throughput Nucleotide Sequencing: methods (MeSH) ; Risk Assessment: methods (MeSH) ; Case-Control Studies (MeSH) ; Prognosis (MeSH) ; Protein Tyrosine Phosphatase, Non-Receptor Type 11: genetics (MeSH) ; Adolescent (MeSH) ; BMP4 ; Abstract word count = 217 ; Biomarker ; Bs-NGS ; DNA methylation ; JMML ; Risk stratification ; Text word count = 3077 ; Bone Morphogenetic Protein 4 ; BMP4 protein, human ; PTPN11 protein, human ; Protein Tyrosine Phosphatase, Non-Receptor Type 11

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Contributing Institute(s):

1. Translationale Medizinische Onkologie (B340)
2. DKTK HD zentral (HD01)
3. DKTK Koordinierungsstelle Freiburg (FR01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2025

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Database coverage:
; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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