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Aim: 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.
Materials & methods: 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.
Results: 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. KBTBD11 clearly differed in methylation and expression between subtypes and before and after remission in TCF3-HLF samples.
Conclusion: KBTBD11 hypomethylation may be a promising potential target for further experimental validation especially for the TCF3-HLF subtype.
Keywords: ALL; DNA methylation; NGS; RNA-Seq; RRBS; epigenetics; epigenomics; leukemia; next-generation sequencing; transcriptomics.