Priyadarshini Kachroo1,2, Silke Szymczak1,3, Femke-Anouska Heinsen1, Michael Forster1, Jörn Bethune1, Georg Hemmrich-Stanisak1, Lewis Baker4, Martin Schrappe5, Martin Stanulla6, Andre Franke1. 1. Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel 24105, Germany. 2. Channing Laboratory, Department of Medicine, Brigham & Women's Hospital & Harvard Medical School, Boston, MA 02115, USA. 3. Institute of Medical Informatics & Statistics, Christian Albrechts University of Kiel, Kiel 24105, Germany. 4. Department of Applied Mathematics, University of Colorado, Boulder, CO 80309, USA. 5. Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel 24105, Germany. 6. Pediatric Hematology & Oncology, Hannover Medical School, Hannover 30625, Germany.
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.
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-PBX1patients 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.
Authors: Juan Carlos Rivera-Mulia; Takayo Sasaki; Claudia Trevilla-Garcia; Naoto Nakamichi; David J H F Knapp; Colin A Hammond; Bill H Chang; Jeffrey W Tyner; Meenakshi Devidas; Jared Zimmerman; Kyle N Klein; Vivek Somasundaram; Brian J Druker; Tanja A Gruber; Amnon Koren; Connie J Eaves; David M Gilbert Journal: Blood Adv Date: 2019-11-12
Authors: Maximilian Schieck; Jana Lentes; Kathrin Thomay; Winfried Hofmann; Yvonne Lisa Behrens; Maike Hagedorn; Juliane Ebersold; Colin F Davenport; Grazia Fazio; Anja Möricke; Swantje Buchmann; Julia Alten; Gunnar Cario; Martin Schrappe; Anke Katharina Bergmann; Martin Stanulla; Doris Steinemann; Brigitte Schlegelberger; Giovanni Cazzaniga; Gudrun Göhring Journal: Ann Hematol Date: 2020-02-20 Impact factor: 3.673