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Loss of IRF8 inhibits the growth of acute myeloid leukemia cells

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Abstract

The transcription factor interferon regulatory factor 8 (IRF8), as a member of the IRF family, is essential for myeloid cell differentiation. However, the precise role of IRF8 in the pathogenesis of acute myeloid leukemia (AML) remains unknown. By using multivariate analysis, we discovered that high IRF8 expression was an independent poor predictor of overall survival (OS) in AML patients from our clinical follow-up study. The proliferation of three AML cell lines was significantly inhibited by shRNA-mediated knockdown of IRF8, owing to cell cycle S-phase arrest. Furthermore, we demonstrated that knocking down IRF8 could suppress the expression of CyclinA and CyclinB1, resulting in a shift in cell cycle distribution. Loss of IRF8 in AML cells decreased the expression of STAT3 and phosphor-STAT3 (pSTAT3), which are key factors in JAK/STAT signal pathway and are important for AML progression. Using a xenograft mouse model, we discovered the antiproliferative effect of losing IRF8 in vivo. In conclusion, this study found that IRF8 may play a prognostic factor and therapeutic target in AML.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This study was funded by the Zhejiang Province Traditional Chinese Medicine Science and Technology Project (2023ZL685), Natural Science Foundation of Ningbo (20221JCGY010278) and Ningbo Medical & Health Leading Academic Discipline Project (2022-S05), China.

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Authors and Affiliations

  1. Department of Hematology, The Affiliated People’s Hospital of Ningbo University, Ningbo, China

    Haihui Zhuang, Fenglin Li, Renzhi Pei, Dong Chen, Xuhui Liu, Shuangyue Li, Peipei Ye, Jiaojiao Yuan, Jiaying Lian & Ying Lu

  2. Institute of Hematology, Ningbo University, Baizhang Road 251#, Ningbo, China

    Haihui Zhuang, Fenglin Li, Renzhi Pei, Dong Chen, Xuhui Liu, Shuangyue Li, Peipei Ye, Jiaojiao Yuan, Jiaying Lian & Ying Lu

  3. College of Life Sciences, China Jiliang University, Hangzhou, China

    Yulian Xu

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  1. Haihui Zhuang
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Contributions

Haihui Zhuang, Fenglin Li, and Ying Lu: research design, data methodology, data interpretation, final manuscript writing, and approval. Yulian Xu, Renzhi Pei, Dong Chen, and Xuhui Liu: literature search, data integration, molecular genetic studies, and approval of the final manuscript. Peipei Ye, Jiaojiao Yuan, and Jiaying Lian: data verification, final manuscript discussion, and approval.

Corresponding author

Correspondence to Ying Lu.

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This study was approved by the Research Ethics Committee of The Affiliated People’s Hospital of Ningbo University. The animal study was approved by the Research Ethics Committee of Ningbo University.

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Haihui Zhuang and Fenglin Li contributed equally to this work.

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Zhuang, H., Li, F., Xu, Y. et al. Loss of IRF8 inhibits the growth of acute myeloid leukemia cells. Ann Hematol 102, 1063–1072 (2023). https://doi.org/10.1007/s00277-023-05156-y

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