Role of microRNAs in glucocorticoid‑resistant B‑cell precursor acute lymphoblastic leukemia

  • Authors:
    • Naoto Sakurai
    • Yoshihiro Komada
    • Ryo Hanaki
    • Mari Morimoto
    • Takahiro Ito
    • Daisuke Nakato
    • Masahiro Hirayama
  • View Affiliations

  • Published online on: June 10, 2019     https://doi.org/10.3892/or.2019.7191
  • Pages: 708-716
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Abstract

Acute lymphoblastic leukemia (ALL) is the most common malignant disorder in children and intensive combination therapy has markedly improved patient prognosis. However, efficacy of the treatment still fails in 10‑15% of patients. Glucocorticoids (GCs) such as prednisone and dexamethasone (DEX) are essential drugs used for ALL chemotherapy, and the response to GC treatment is a strong independent factor of ALL prognosis. In the present study, we examined the mechanism of GC resistance of B‑cell precursor ALL (BCP‑ALL). As determined by RT‑qPCR and western blot analyses, GC treatment upregulated glucocorticoid receptor (GR) protein and Bcl‑2‑interacting mediator of cell death (BCL2L11, BIM) protein expression, resulting in apoptosis of a GC‑sensitive BCP‑ALL cell line, but not of a GC‑resistant BCP‑ALL cell line as shown by flow cytometry. GR was downregulated in a DEX‑resistant BCP‑ALL cell line which was induced by treatment of cells with increasing concentrations of DEX. Importantly, expression levels of miR‑142‑3p and miR‑17~92 cluster were upregulated in the BCP‑ALL cell line with acquired DEX resistance as examined by RT‑qPCR. Our results suggest that interference of miR‑142‑3p and miR‑17~92 may overcome the resistance of BCP‑ALL to GCs.

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August 2019
Volume 42 Issue 2

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Online ISSN:1791-2431

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Copy and paste a formatted citation
APA
Sakurai, N., Komada, Y., Hanaki, R., Morimoto, M., Ito, T., Nakato, D., & Hirayama, M. (2019). Role of microRNAs in glucocorticoid‑resistant B‑cell precursor acute lymphoblastic leukemia. Oncology Reports, 42, 708-716. https://doi.org/10.3892/or.2019.7191
MLA
Sakurai, N., Komada, Y., Hanaki, R., Morimoto, M., Ito, T., Nakato, D., Hirayama, M."Role of microRNAs in glucocorticoid‑resistant B‑cell precursor acute lymphoblastic leukemia". Oncology Reports 42.2 (2019): 708-716.
Chicago
Sakurai, N., Komada, Y., Hanaki, R., Morimoto, M., Ito, T., Nakato, D., Hirayama, M."Role of microRNAs in glucocorticoid‑resistant B‑cell precursor acute lymphoblastic leukemia". Oncology Reports 42, no. 2 (2019): 708-716. https://doi.org/10.3892/or.2019.7191