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    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.

    Citation

    Radosław Chaber, Artur Gurgul, Jacek Tabarkiewicz, Grażyna Wróbel, Tomasz Szmatoła, Igor Jasielczuk, Olga Haus, Monika Lejman, Blanka Rybka, Renata Ryczan-Krawczyk, Anna Jaśkowiec, Sylwia Paszek, Natalia Potocka, Christopher J Arthur, Wioletta Bal, Kornelia Łach, Aneta Kowal, Izabela Zawlik, Elżbieta Latos-Grażyńska. MicroRNA gene methylation landscape in pediatric B-cell precursor acute lymphoblastic leukemia. Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 2022 Mar;31(3):293-305

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    PMID: 35092653

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