Overexpression of IFIT2 inhibits the proliferation of chronic myeloid leukemia cells by regulating the BCR‑ABL/AKT/mTOR pathway

Zhang,Zhanglin; Li,Na; Liu,Shuyuan; Jiang,Mei; Wan,Jinghua; Zhang,Yonglu; Wan,Lagen; Xie,Caifeng; Le,Aiping

doi:10.3892/ijmm.2020.4500

Overexpression of IFIT2 inhibits the proliferation of chronic myeloid leukemia cells by regulating the BCR‑ABL/AKT/mTOR pathway

Authors:
- Zhanglin Zhang
- Na Li
- Shuyuan Liu
- Mei Jiang
- Jinghua Wan
- Yonglu Zhang
- Lagen Wan
- Caifeng Xie
- Aiping Le
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Affiliations: Department of Blood Transfusion, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Stomatology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Clinal Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, School of Basic Medical Sciences, Nanchang University, Nanchang, Jiangxi 330031, P.R. China
Published online on: February 13, 2020 https://doi.org/10.3892/ijmm.2020.4500
Pages: 1187-1194

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Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative disorder that accounts for ~10% of all newly diagnosed leukemia cases. Early diagnosis is essential for long‑term beneficial outcomes. The present study observed that interferon‑induced protein with tetratricopeptde repeats 2 (IFIT2) expression levels were reduced in bone marrow samples from CML patients compared with control samples using RNA sequencing and reverse transcription‑PCR. IFIT2 expression levels were restored in patients treated with tyrosine kinase inhibitors. To investigate the effect of IFIT2 on CML patients, a stable IFIT2 expressing K562 cell line was established. It was demonstrated that IFIT2 overexpression in K562 cells inhibits cell proliferation and arrests the cell cycle at the G1 phase. In addition, it was demonstrated by western blotting that IFIT2 inhibits the BCR‑ABL oncoprotein and regulates its downstream AKT/mTOR signaling pathway. IFIT2 could induce cell cycle arrest‑associated gene p27kip1 by degrading cullin1‑mediated E3 ligases. In summary, the present study demonstrated that IFIT2 was efficacious in inhibiting CML and is a potential therapeutic target.

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