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Cross-sectional network analysis of plasma proteins/metabolites correlated with pathogenesis and therapeutic response in acute promyelocytic leukemia

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Abstract

The treatment of PML/RARA+ acute promyelocytic leukemia (APL) with all-trans-retinoic acid and arsenic trioxide (ATRA/ATO) has been recognized as a model for translational medicine research. Though an altered microenvironment is a general cancer hallmark, how APL blasts shape their plasma composition is poorly understood. Here, we reported a cross-sectional correlation network to interpret multilayered datasets on clinical parameters, proteomes, and metabolomes of paired plasma samples from patients with APL before or after ATRA/ATO induction therapy. Our study revealed the two prominent features of the APL plasma, suggesting a possible involvement of APL blasts in modulating plasma composition. One was characterized by altered secretory protein and metabolite profiles correlating with heightened proliferation and energy consumption in APL blasts, and the other featured APL plasma-enriched proteins or enzymes catalyzing plasma-altered metabolites that were potential trans-regulatory targets of PML/RARA. Furthermore, results indicated heightened interferon-gamma signaling characterizing a tumor-suppressing function of the immune system at the first hematological complete remission stage, which likely resulted from therapy-induced cell death or senescence and ensuing supraphysiological levels of intracellular proteins. Overall, our work sheds new light on the pathophysiology and treatment of APL and provides an information-rich reference data cohort for the exploratory and translational study of leukemia microenvironment.

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Acknowledgements

This study was supported by the State Key Laboratory of Medical Genomics, the Double First-Class Project (No. WF510162602) from the Ministry of Education, the Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research (No. 2019CXJQ01), the Overseas Expertise Introduction Project for Discipline Innovation (111 Project; No. B17029), the National Natural Science Foundation of China (Nos. 82230006 and 32170663), the Shanghai Clinical Research Center for Hematological disease (No. 19MC1910700), the Shanghai Shenkang Hospital Development Center (No. SHDC2020CR5002), the Shanghai Major Project for Clinical Medicine (No. 2017ZZ01002), the Innovative Research Team of High-level Local Universities in Shanghai and the Yangfan Program of the Science and Technology Commission of Shanghai Municipality (No. 22YF1425500). We thank all members of the Shanghai Institute of Hematology and the National Research Center for Translational Medicine at Shanghai.

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  1. These authors contributed equally.

Authors and Affiliations

  1. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Niu Qiao, Yizhu Lyu, Feng Liu, Yuliang Zhang, Xiaolin Ma, Xiaojing Lin, Junyu Wang, Yinyin Xie, Ruihong Zhang, Jing Qiao, Hongming Zhu, Li Chen, Hai Fang, Tong Yin, Zhu Chen, Qiang Tian & Saijuan Chen

  2. Department of Hematology, Second Hospital of Dalian Medical University, Dalian, 116021, China

    Yizhu Lyu

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  1. Niu Qiao
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Correspondence to Feng Liu, Tong Yin, Qiang Tian or Saijuan Chen.

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Conflict of interests Niu Qiao, Yizhu Lyu, Feng Liu, Yuliang Zhang, Xiaolin Ma, Xiaojing Lin, Junyu Wang, Yinyin Xie, Ruihong Zhang, Jing Qiao, Hongming Zhu, Li Chen, Hai Fang, Tong Yin, Zhu Chen, and Qiang Tian declare no competing interests. Saijuan Chen is the Editor-in-Chief of Frontiers of Medicine, who was excluded from the peer-review process and all editorial decisions related to the acceptance and publication of this article. Peer-review was handled independently by the other editors to minimize bias.

The study was approved by Ethics Committee, Rui Jin Hospital, and the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent was obtained from all patients for being included in the study.

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Cross-sectional network analysis of plasma proteins/metabolites correlated with pathogenesis and therapeutic response in acute promyelocytic leukemia

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Qiao, N., Lyu, Y., Liu, F. et al. Cross-sectional network analysis of plasma proteins/metabolites correlated with pathogenesis and therapeutic response in acute promyelocytic leukemia. Front. Med. (2023). https://doi.org/10.1007/s11684-023-1022-x

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