NGS-based methylation profiling differentiates TCF3-HLF and TCF3-PBX1 positive B-cell acute lymphoblastic leukemia. (February 2018)

• Record Type: Journal Article
• Authors: Kachroo, Priyadarshini; Szymczak, Silke; Heinsen, Femke-Anouska; Forster, Michael; Bethune, Jörn; Hemmrich-Stanisak, Georg; Baker, Lewis; Schrappe, Martin; Stanulla, Martin; Franke, Andre
• Is Part Of: Epigenomics. Volume 10:Number 2(2018)
• Page Start: 133
• Page End: 147
• Publication Date: 2018-02
• Subjects: ALL -- DNA methylation -- epigenetics -- epigenomics -- leukemia -- next-generation sequencing -- NGS -- RNA-Seq -- RRBS -- transcriptomics; Epigenesis -- Periodicals; Genomics -- Periodicals; Chromatin -- Periodicals; DNA -- Periodicals; 572.87
• DOI: 10.2217/epi-2017-0080
• Languages: English
• ISSNs: 1750-1911

Abstract

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.