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

Abstract : 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.
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Submitted on : Thursday, December 27, 2018 - 11:46:43 AM
Last modification on : Wednesday, July 24, 2019 - 1:21:13 AM

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Ismael Soltani, Kais Douzi, Hanen Gharbi, Islem Benhassine, Mouheb Teber, et al.. Downregulation of miR-451 in Tunisian chronic myeloid leukemia patients: potential implication in imatinib resistance. Hematology, Maney Publishing, 2017, 22 (4), pp.201-207. ⟨10.1080/10245332.2016.1252020⟩. ⟨pasteur-01965980⟩

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