Open Access

Knockdown of ribonucleotide reductase regulatory subunit M2 increases the drug sensitivity of chronic myeloid leukemia to imatinib‑based therapy

  • Authors:
    • Chunshui Liu
    • Yuying Li
    • Ruiping Hu
    • Wei Han
    • Sujun Gao
  • View Affiliations

  • Published online on: June 11, 2019     https://doi.org/10.3892/or.2019.7194
  • Pages: 571-580
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Imatinib‑based targeted treatment is the standard therapy for chronic myeloid leukemia (CML); however, drug resistance is an inevitable issue for imatinib‑based CML treatment. Imatinib resistance can be ascribed to Bcr‑Abl‑dependent and independent resistance. In the present study, peripheral blood samples were collected from imatinib‑sensitive (IS) and imatinib‑resistant (IR) CML patients and transcriptome sequencing was carried out. From the RNA‑seq data, a significantly altered IR‑related gene (IRG), ribonucleotide reductase regulatory subunit M2 (RRM2) was identified. Using real‑time quantitative fluorescence PCR (qF‑PCR), we found that RRM2 was elevated in both IR CML patients and an IR cell line. Using reverse‑transcription PCR (RT‑PCR) and western blot analysis, we indicated that imatinib can increase RRM2 level in a dose‑dependent manner in IR cells. We also demonstrated that RRM2 is involved in the Bcl‑2/caspase cell apoptotic pathway and in the Akt cell signaling pathway, and therefore affects the cell survival following imatinib therapy. The present study, for the first time, indicates that RRM2 is responsible for drug resistance in imatinib‑based therapy. Therefore, RRM2 gene can be considered as a potential therapeutic target in the clinical treatment of CML.

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August 2019
Volume 42 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Copy and paste a formatted citation
APA
Liu, C., Li, Y., Hu, R., Han, W., & Gao, S. (2019). Knockdown of ribonucleotide reductase regulatory subunit M2 increases the drug sensitivity of chronic myeloid leukemia to imatinib‑based therapy. Oncology Reports, 42, 571-580. https://doi.org/10.3892/or.2019.7194
MLA
Liu, C., Li, Y., Hu, R., Han, W., Gao, S."Knockdown of ribonucleotide reductase regulatory subunit M2 increases the drug sensitivity of chronic myeloid leukemia to imatinib‑based therapy". Oncology Reports 42.2 (2019): 571-580.
Chicago
Liu, C., Li, Y., Hu, R., Han, W., Gao, S."Knockdown of ribonucleotide reductase regulatory subunit M2 increases the drug sensitivity of chronic myeloid leukemia to imatinib‑based therapy". Oncology Reports 42, no. 2 (2019): 571-580. https://doi.org/10.3892/or.2019.7194