Abstract

Acute lymphoblastic leukaemia (ALL) is the most common form of paediatric cancer and epigenetic aberrations are determinants of leukaemogenesis. The aim of this study was to investigate the methylation degree of a distinct phospholipase A2 receptor 1 (PLA2R1) promoter region in paediatric ALL patients and to evaluate its relevance as new biomarker for monitoring treatment response and burden of residual disease. The impact of PLA2R1 re-expression on proliferative parameters was assessed in vitro in Jurkat cells with PLA2R1 naturally silenced by DNA methylation. Genomic DNA was isolated from bone marrow (BM) and peripheral blood (PB) of 44 paediatric ALL patients. PLA2R1 methylation was analysed using digital PCR and compared to 20 healthy controls. Transfected Jurkat cells were investigated using cell growth curve analysis and flow cytometry. PLA2R1 was found hypermethylated in BM and PB from pre-B and common ALL patients, and in patients with the disease relapse. PLA2R1 methylation decreased along with leukaemic blast cell reduction during ALL induction treatment. In vitro analysis revealed an anti-proliferative phenotype associated with PLA2R1 re-expression, suggesting a tumour-suppressive function of PLA2R1. Collected data indicates that PLA2R1 promoter methylation quantitation can be used as biomarker for ALL induction treatment control, risk stratification, and early detection of ALL relapse.

Details

Title
Methylation of the Phospholipase A2 Receptor 1 Promoter Region in Childhood B Cell Acute Lymphoblastic Leukaemia
Author
Friedemann, Markus 1 ; Gutewort Katharina 1 ; Thiem, Dana 1 ; Nacke Brit 1 ; Jandeck Carsten 1 ; Lange, Björn Sönke 2 ; Sukocheva Olga 3   VIAFID ORCID Logo  ; Suttorp Meinolf 4   VIAFID ORCID Logo  ; Menschikowski Mario 5 

1  University Hospital Carl Gustav Carus, Technical University of Dresden, Institute of Clinical Chemistry and Laboratory Medicine, Dresden, Germany 
2  University Hospital Carl Gustav Carus, Technical University of Dresden, Department of Paediatrics, Dresden, Germany 
3  Flinders University of South Australia, School of Health Sciences, Bedford Park, Australia (GRID:grid.1014.4) (ISNI:0000 0004 0367 2697) 
4  Medical Faculty, Paediatric Haemato-Oncology, Technical University, Dresden, Germany (GRID:grid.4488.0) (ISNI:0000 0001 2111 7257) 
5  University Hospital Carl Gustav Carus, Technical University of Dresden, Institute of Clinical Chemistry and Laboratory Medicine, Dresden, Germany (GRID:grid.4488.0) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-020-65825-0
ProQuest document ID
2409175115
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.