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

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

doi:10.2217/epi-2017-0080

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

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

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

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.

Original language	English (US)
Pages (from-to)	133-147
Number of pages	15
Journal	Epigenomics
Volume	10
Issue number	2
DOIs	https://doi.org/10.2217/epi-2017-0080
State	Published - Feb 2018
Externally published	Yes

All Science Journal Classification (ASJC) codes

Genetics
Cancer Research

Keywords

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

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10.2217/epi-2017-0080

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

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.",

keywords = "ALL, DNA methylation, epigenetics, epigenomics, leukemia, next-generation sequencing, NGS, RNA-Seq, RRBS, transcriptomics",

author = "Priyadarshini Kachroo and Silke Szymczak and Heinsen, {Femke Anouska} and Michael Forster and J{\"o}rn Bethune and Georg Hemmrich-Stanisak and Lewis Baker and Martin Schrappe and Martin Stanulla and Andre Franke",

note = "Publisher Copyright: {\textcopyright} 2018 Future Medicine Ltd.",

year = "2018",

month = feb,

doi = "10.2217/epi-2017-0080",

language = "English (US)",

volume = "10",

pages = "133--147",

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T1 - NGS-based methylation profiling differentiates TCF3-HLF and TCF3-PBX1 positive B-cell acute lymphoblastic leukemia

AU - Kachroo, Priyadarshini

AU - Szymczak, Silke

AU - Heinsen, Femke Anouska

AU - Forster, Michael

AU - Bethune, Jörn

AU - Hemmrich-Stanisak, Georg

AU - Baker, Lewis

AU - Schrappe, Martin

AU - Stanulla, Martin

AU - Franke, Andre

PY - 2018/2

Y1 - 2018/2

N2 - 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.

AB - 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.

KW - ALL

KW - DNA methylation

KW - epigenetics

KW - epigenomics

KW - leukemia

KW - next-generation sequencing

KW - NGS

KW - RNA-Seq

KW - RRBS

KW - transcriptomics

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ER -

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

Abstract

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