NGS-based methylation profiling differentiates TCF3-HLF and TCF3-PBX1 positive B-cell acute lymphoblastic leukemia

• Published in: Epigenomics Vol. 10; no. 2; pp. 133 - 147
• Main Authors: Kachroo, Priyadarshini, Szymczak, Silke, Heinsen, Femke-Anouska, Forster, Michael, Bethune, Jörn, Hemmrich-Stanisak, Georg, Baker, Lewis, Schrappe, Martin, Stanulla, Martin, Franke, Andre
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.02.2018
• Subjects: Acute lymphoblastic leukemia; Adolescent; ALL; Apoptosis; B-Lymphocytes - metabolism; Biomarkers; Bisulfite; Bone marrow; Breast cancer; Cancer therapies; Cell cycle; Chemotherapy; Child; Colorectal cancer; CpG Islands; Deoxyribonucleic acid; Disease; DNA; DNA Methylation; Epigenesis, Genetic; Epigenetics; epigenomics; Gene Expression; Gene sequencing; Genomes; Humans; Leukemia; Lymphatic leukemia; Lymphocytes B; Medical prognosis; next-generation sequencing; NGS; Oncogene Proteins, Fusion - biosynthesis; Oncogene Proteins, Fusion - genetics; Patients; Pediatrics; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - immunology; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - metabolism; Remission; Ribonucleic acid; RNA; RNA-Seq; RRBS; Transcription factors; transcriptomics; ALL; leukemia; RNA-Seq; next-generation sequencing; RRBS; DNA methylation; transcriptomics; epigenomics; NGS; epigenetics
• ISSN: 1750-1911; 1750-192X; 1750-192X
• DOI: 10.2217/epi-2017-0080

To determine whether methylation differences between mostly fatal TCF3-HLF and curable TCF3-PBX1 pediatric acute lymphoblastic leukemia subtypes can be associated with differential gene expression and remission. Five (extremely rare) TCF3-HLF versus five (very similar) TCF3-PBX1 patients were sampled before and after remission and analyzed using reduced representation bisulfite sequencing and RNA-sequencing. We identified 7000 differentially methylated CpG sites between subtypes, of which 78% had lower methylation levels in TCF3-HLF. Gene expression was negatively correlated with CpG sites in 23 genes. clearly differed in methylation and expression between subtypes and before and after remission in TCF3-HLF samples. hypomethylation may be a promising potential target for further experimental validation especially for the TCF3-HLF subtype.