Methylation of the Phospholipase A2 Receptor 1 Promoter Region in Childhood B Cell Acute Lymphoblastic Leukaemia

• Published in: Scientific reports Vol. 10; no. 1; p. 9058
• Main Authors: Friedemann, Markus, Gutewort, Katharina, Thiem, Dana, Nacke, Brit, Jandeck, Carsten, Lange, Björn Sönke, Sukocheva, Olga, Suttorp, Meinolf, Menschikowski, Mario
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.06.2020; Nature Publishing Group
• Subjects: 45; 45/77; 45/90; 631/67/1857; 692/4028/67/1990; Acute lymphoblastic leukemia; Adolescent; Biomarkers; Biomarkers, Tumor - genetics; Bone marrow; Cell Line, Tumor; Child; Child, Preschool; Childhood; Children; Deoxyribonucleic acid; DNA; DNA methylation; DNA Methylation - genetics; Epigenetics; Female; Flow cytometry; Gene Expression Regulation, Neoplastic - genetics; Humanities and Social Sciences; Humans; Infant; Jurkat Cells; Leukemia; Male; multidisciplinary; Neoplasm Recurrence, Local - genetics; Peripheral blood; Phenotypes; Phospholipase A2; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Promoter Regions, Genetic - genetics; Quantitation; Receptors, Phospholipase A2 - genetics; Science; Science (multidisciplinary); Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-65825-0

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.