1. MicroRNA gene methylation landscape in pediatric B-cell precursor acute lymphoblastic leukemia.
- Author
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Chaber R, Gurgul A, Tabarkiewicz J, Wróbel G, Szmatoła T, Jasielczuk I, Haus O, Lejman M, Rybka B, Ryczan-Krawczyk R, Jaśkowiec A, Paszek S, Potocka N, Arthur CJ, Bal W, Łach K, Kowal A, Zawlik I, and Latos-Grażyńska E
- Subjects
- Child, DNA Methylation, Humans, Methylation, Promoter Regions, Genetic, MicroRNAs genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma pathology, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics
- Abstract
Background: Aberrant DNA methylation is an important mechanism by which the normal patterns of microRNA expression are disrupted in human cancers including B-cell precursor acute lymphoblastic leukemia (BCP ALL), the most common pediatric malignancy., Objectives: To characterize the methylation profile landscape of microRNA genes in BCP ALL patients., Material and Methods: We employed Infinium® MethylationEPIC BeadChip Arrays to measure the methylation of microRNA genes from bone marrow samples of children with BCP ALL (n = 38) and controls without neoplasms (n = 4)., Results: This analysis revealed differential methylation of the microRNA genes in the pediatric BCP ALL when compared to the control. A subcluster amongst BCP ALL patients with TCF3-PBX1 genetic subtype was also observed. No other differences were observed in association with age, gender or risk group. Several interesting leukemia-related phenotypes are enriched by the genes with hyperand hypomethylated sites located in promoters as well as gene bodies. The top 3 miRNA genes, promoters of which were the most statistically significantly hypermethylated in BCP ALL were MIR1273G, MIR1304 and MIR663, and the top 3 hypomethylated were MIR4442, MIR155 and MIR3909., Conclusions: In this study, a different microRNA genes methylation landscape was shown in pediatric BCP ALL compared to children without neoplasms. A visible subcluster among BCP ALL samples consisted of individuals with TCF3-PBX1 genetic subtype. No other differences were observed in association with age, gender or risk group. Several interesting leukemia-connected phenotypes were found, associated with genes with hyperand hypomethylated sites located on promoters as well as gene bodies.
- Published
- 2022
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