MicroRNA gene methylation landscape in pediatric B-cell precursor acute lymphoblastic leukemia

• Published in: Advances in clinical and experimental medicine : official organ Wroclaw Medical University Vol. 31; no. 3; pp. 293 - 305
• Main Authors: Chaber, Radosław, Gurgul, Artur, Tabarkiewicz, Jacek, Wróbel, Grażyna, Szmatoła, Tomasz, Jasielczuk, Igor, Haus, Olga, Lejman, Monika, Rybka, Blanka, Ryczan-Krawczyk, Renata, Jaśkowiec, Anna, Paszek, Sylwia, Potocka, Natalia, Arthur, Christopher J, Bal, Wioletta, Łach, Kornelia, Kowal, Aneta, Zawlik, Izabela, Latos-Grażyńska, Elżbieta
• Format: Journal Article
• Language: English
• Published: Poland 01.03.2022
• Subjects: Child; DNA Methylation; Humans; Methylation; MicroRNAs - genetics; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Promoter Regions, Genetic; microRNA; children; BCP ALL; methylation
• ISSN: 1899-5276
• DOI: 10.17219/ACEM/144170

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. To characterize the methylation profile landscape of microRNA genes in BCP ALL patients. 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). 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. 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.