Jab1 promotes immune evasion and progression in acute myeloid leukemia models under oxidative stress

Nan Zhang; Qian Wang; Guopeng Chen; Li Liu; Zhiying Wang; Linlu Ma; Yuxing Liang; Jinxian Wu; Xinqi Li; Xiaoyan Liu; Fuling Zhou

doi:10.1172/JCI183761

¹Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China

²College of Chemistry and Molecular Sciences, Wuhan university, Wuhan, China

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¹Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China

²College of Chemistry and Molecular Sciences, Wuhan university, Wuhan, China

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¹Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China

²College of Chemistry and Molecular Sciences, Wuhan university, Wuhan, China

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¹Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China

²College of Chemistry and Molecular Sciences, Wuhan university, Wuhan, China

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¹Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China

²College of Chemistry and Molecular Sciences, Wuhan university, Wuhan, China

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¹Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China

²College of Chemistry and Molecular Sciences, Wuhan university, Wuhan, China

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¹Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China

²College of Chemistry and Molecular Sciences, Wuhan university, Wuhan, China

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¹Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China

²College of Chemistry and Molecular Sciences, Wuhan university, Wuhan, China

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¹Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China

²College of Chemistry and Molecular Sciences, Wuhan university, Wuhan, China

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¹Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China

²College of Chemistry and Molecular Sciences, Wuhan university, Wuhan, China

Find articles by Liu, X. in: PubMed | Google Scholar

¹Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China

²College of Chemistry and Molecular Sciences, Wuhan university, Wuhan, China

Find articles by Zhou, F. in: PubMed | Google Scholar

J Clin Invest. https://doi.org/10.1172/JCI183761.
Copyright © 2025, Zhang et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Published August 5, 2025 - Version history

Acute myeloid leukemia (AML) is the most common hematological malignancy. Leukemia stem cells exhibit high levels of oxidative stress, with reactive oxygen species (ROS) being the primary products of this stress, inducing the expression of Jab1. Previous studies have demonstrated that Jab1, as a transcriptional coactivator of c-JUN, promotes the malignant progression of AML under oxidative stress. However, its role in immune evasion is still under investigation. Here, we observed that knocking out Jab1 reduced the expression of immune checkpoints in vivo, effectively overcame the immune evasion of AML. Interestingly, the deletion of Jab1 had no impact on the maturation of normal hematopoietic cells in mice. Mechanistically, Jab1 directly activated IGF2BP3 by driving the transcription factor c-JUN, consequently modulated the m⁶A modification of LILRB4 mRNA and promoted immune evasion in AML. Finally, CSN5i-3 effectively disrupted the signaling pathway mediated by Jab1, thereby restoring cellular immune surveillance and halting the progression of AML. Thus, our results highlight the functional role of Jab1 in supporting AML survival and support the development of targeted therapeutic strategies.

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Jab1 promotes immune evasion and progression in acute myeloid leukemia models under oxidative stress

Nan Zhang,¹ Qian Wang,¹ Guopeng Chen,¹ Li Liu,¹ Zhiying Wang,² Linlu Ma,¹ Yuxing Liang,¹ Jinxian Wu,¹ Xinqi Li,¹ Xiaoyan Liu,¹ and Fuling Zhou¹

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Jab1 promotes immune evasion and progression in acute myeloid leukemia models under oxidative stress

Nan Zhang,1 Qian Wang,1 Guopeng Chen,1 Li Liu,1 Zhiying Wang,2 Linlu Ma,1 Yuxing Liang,1 Jinxian Wu,1 Xinqi Li,1 Xiaoyan Liu,1 and Fuling Zhou1

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Nan Zhang,¹ Qian Wang,¹ Guopeng Chen,¹ Li Liu,¹ Zhiying Wang,² Linlu Ma,¹ Yuxing Liang,¹ Jinxian Wu,¹ Xinqi Li,¹ Xiaoyan Liu,¹ and Fuling Zhou¹