Downregulation of miR-451 in Tunisian chronic myeloid leukemia patients: potential implication in imatinib resistance

Hematology. 2017 May;22(4):201-207. doi: 10.1080/10245332.2016.1252020. Epub 2016 Nov 9.


Objectives: Resistance to imatinib has been recognized as a major challenge for the treatment of chronic myeloid leukemia (CML). Aberrant expression of miR-451 has been reported to participate in anticancer drug resistance. However, the role of miR-451 in imatinib resistance has not been investigated. The present study was undertaken to determine the expression of miR-451 in order to find a possible association between the expression of this miRNA and imatinib resistance in Tunisian CML patients.

Methods: First, real-time RT-PCR was performed to identify the expression of miR-451 in peripheral leukocytes of 59 CML patients treated with imatinib. Then, bioinformatics analysis was carried out to understand the regulatory roles of miR-451 in imatinib-resistant process.

Results: Downregulated miR-451 was observed in imatinib-resistant CML cases. In silico analysis identified MYC as a potential target of miR-451. We further revealed the existence of an MYC-binding site in MiR-451 promoter region. On the other hand, increased level of MYC was detected in imatinib-resistant CML cases which may explain the causative role of MYC in CML cases and the downregulation of miR-451.

Conclusion and discussion: Taken together, our findings suggest that miR-451 and MYC form together a regulatory loop which may act as a potential therapeutic target, and disruption of suggested regulatory loop could help to improve CML therapy.

Keywords: Chronic myeloid leukemia; MYC; imatinib mesylate; miR-451; resistance.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Base Sequence
  • Computational Biology
  • Down-Regulation
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Imatinib Mesylate / pharmacology*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / blood
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukocytes / metabolism
  • Male
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • Real-Time Polymerase Chain Reaction
  • Tunisia


  • Antineoplastic Agents
  • MIRN451 microRNA, human
  • MYC protein, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-myc
  • Imatinib Mesylate