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

作者：Kachroo Priyadarshini; Szymczak Silke; Heinsen Femke Anouska; Forster Michael; Bethune Joern; Hemmrich Stanisak Georg; Baker Lewis; Schrappe Martin; Stanulla Martin^*; Franke Andre

来源：Epigenomics, 2018, 10(2): 133-147.

DOI：10.2217/epi-2017-0080

• ALL
• DNA methylation
• epigenetics
• epigenomics
• leukemia
• next-generation sequencing
• NGS
• RNA-Seq
• RRBS
• transcriptomics

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.

• 出版日期2018-2