Selected miRNA levels are associated with IKZF1 microdeletions in pediatric acute lymphoblastic leukemia

特定 miRNA 水平与儿童急性淋巴细胞白血病中的 IKZF1 微缺失相关

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作者:J Krzanowski, J Madzio, A Pastorczak, A Tracz, M Braun, J Tabarkiewicz, A Pluta, W Młynarski, I Zawlik

Abstract

The clinical outcome of children with high-risk relapsed B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is poor. The present study assessed the utility and prognostic value of selected microRNA (miRNA/miR) in BCP-ALL. The changes in the expression levels of these miRNAs regarding known gene lesions affecting lymphoid development [early B-cell factor 1 (EBF1), ETS variant 6 (ETV6), IKAROS family zinc finger 1 (IKZF1), paired box 5 (PAX5), cyclin dependent kinase inhibitor (CDKN) 2A/CDKN2B, retinoblastoma 1 (RB1), pseudoautosomal region 1 (PAR1), B-cell translocation gene 1 protein (BTG1)] were analyzed. The following miRNAs were analyzed: miR-24, miR-31, miR-128, miR-542, and miR-708. The present study focused on patients with deletions of the IKAROS transcriptional factor gene IKZF1, which is currently considered to be an independent negative prognostic factor for ALL outcome. It was demonstrated that the expression level of miR-128 was significantly lower in patients with IKZF1 deletion compared with patients without IKZF1 deletion. Additionally, low expression of miR-542 was associated with CDKN2A/B and miR-31deletions, and low expression of miR-24 was associated with miR-31 deletion. Low expression of miR-31, miR-24, miR-708 and miR-128 was associated with PAX5 deletion, high expression of miR-24 and miR-542 was associated with PAR1 deletion and high expression of miR-708 was associated with ETV6 deletion. The expression of the selected miRNAs was not associated with deletions of BTG1, EBF1 and RB1. These data, by emphasizing the association of miRNAs expression level with microdeletions, may assist to elucidate ALL biology and contribute to future studies on the possible applications of the miRNA profile for diagnosis.

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