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

Title of publication: 

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

Authors: 

Priyadarshini Kachroo, Silke Szymczak , Femke-Anouska Heinsen, Michael Forster, Jörn Bethune, Georg Hemmrich-Stanisak, Lewis Baker, Martin Schrappe, Martin Stanulla, Andre Franke

Year of Publication: 

2018 Feb. Epub 2018 Jan 15.

medium resp. publishing house / place: 

Epigenomics .

edition / issue: 

10 (2)

Pages: 

133-147

related to project: 

Genome-wide mapping of the inflammation methylome I

Pubmed: 

Pubmed - PMID 29334255

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.

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