Comprehensive Epigenome-Wide Profiling Reveals Distinctive DNA Methylation Signatures and Potential Prognostic Biomarkers in Mexican Pediatric B-ALL
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. In Mexico, its higher incidence and lower survival suggest a role for epigenetic factors like DNA methylation (DNAme). We conducted an epigenome-wide association study (EWAS) to define the methylation landscape and identify the profiles associated with ALL and relapse. Bone marrow or peripheral blood samples from pediatric ALL patients at diagnosis and controls without ALL were analyzed using an Infinium MethylationEPIC v2.0 array. Differential methylation was assessed using the ChAMP package. We identified a significant hypermethylated profile in ALL patients compared to controls. Probes in <i>MAD1L1</i> and <i>RPTOR</i> contained the most differentially methylated CpG sites. Key affected pathways included proliferation, neurotransmission, and neuronal signaling. Survival analysis revealed that hypomethylation of four specific CpGs-cg01052776 (<i>RNH1</i>), cg20747787, cg05001671, and cg01767116 (<i>FBXL22</i>)-was significantly associated with an increased risk of relapse, highlighting their potential as prognostic biomarkers. This study underscores the importance of epigenetic mechanisms in pediatric ALL.
Authors
- Haydeé Rosas‐Vargas (ORCID: https://orcid.org/0000-0003-0635-8284)
- Laura Elizabeth Merino‐Pasaye
- Janet Flores‐Lujano (ORCID: https://orcid.org/0000-0003-0727-2837)
- José Refugio Torres‐Nava
- Francisco Xavier Guerra‐Castillo (ORCID: https://orcid.org/0000-0002-3346-2004)
- Juan Carlos Núñez-Enríquez (ORCID: https://orcid.org/0000-0002-8070-9727)
- Silvia Jiménez‐Morales (ORCID: https://orcid.org/0000-0002-6590-9712)
- Martha Margarita Velázquez‐Aviña
- Rosa Martha Espinosa‐Elizondo
- Mónica Ortiz-Maganda
- Elva Jiménez‐Hernández
- Maria Luisa Pérez‐Saldívar (ORCID: https://orcid.org/0000-0002-9987-2479)
- José Gabriel Peñaloza‐González
- Luz Victoria Flores‐Villegas (ORCID: https://orcid.org/0000-0002-0676-9617)
- Aurora Medina‐Sansón (ORCID: https://orcid.org/0000-0002-1818-8879)
- Vilma Carolina Bekker‐Méndez (ORCID: https://orcid.org/0000-0002-6161-1425)
- Eva Ramón‐Gallegos (ORCID: https://orcid.org/0000-0003-2262-5207)
- Jorge Alfonso Martín‐Trejo (ORCID: https://orcid.org/0000-0002-1323-1575)
- Minerva Mata‐Rocha (ORCID: https://orcid.org/0000-0003-0949-461X)
- Omar Alejandro Sepúlveda‐Robles (ORCID: https://orcid.org/0000-0003-2152-3954)
- Jorge Meléndez-Zajgla (ORCID: https://orcid.org/0000-0002-2209-1607)
- David Aldebarán Duarte-Rodríguez (ORCID: https://orcid.org/0000-0002-0560-2540)
- Juan Manuel Mejía‐Aranguré (ORCID: https://orcid.org/0000-0001-8027-6231)
- Alan Alberto Fong-López (ORCID: https://orcid.org/0000-0002-2118-7287)
- Georgina Jiménez-Morales
Institutions
- Mexican Social Security Institute (MX)
- Universidad Autónoma de Sinaloa (MX)
- Hospital General de México (MX)
- Centro Médico Nacional La Raza (MX)
- Secretaria de Salud (MX)
- Hospital Infantil de México Federico Gómez (MX)
- National Institute of Genomic Medicine (MX)
- Secretaria de Salud (HN)
- Centro Medico Nacional Siglo XXI (MX)
- Hospital Pediátrico Moctezuma (MX)
- Instituto de Medicina Genómica (ES)
- Hospital Juárez de México (MX)
- Instituto Politécnico Nacional (MX)
- Institute for Social Security and Services for State Workers (MX)
- Universidad Nacional Autónoma de México (MX)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2025-10-22
- DOI
- https://doi.org/10.3390/ijms262110261
- Citations
- 1
- Primary Topic
- Acute Lymphoblastic Leukemia research
- Type
- article
- Field-Weighted Citation Impact
- 1.88