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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1547289
This article is part of the Research TopicMyelodysplastic Neoplasm and Acute Myeloid Leukemia: Multi-Omics Approaches and Precision MedicineView all 3 articles
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Background: Aplastic anemia (AA), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML) exhibit complex pathogenic mechanisms and interrelated characteristics. We aimed to identify the common hub genes, establishing a foundation for preventing disease progression.Methods: We selected relevant datasets from the Gene Expression Omnibus(GEO) database for differential gene expression, gene set enrichment, and weighted gene co-expression network analyses to identify hub genes, and then validated them. Subsequent analyses included immune infiltration analysis, single-cell sequencing, and cell communication analysis. We performed Mendelian randomization to screen inflammatory factors and immune cells. We used RT-qPCR, Enzyme - Linked Immunosorbent Assay(ELISA), and cell proliferation assays to validate the identified hub genes, their relationship with cellular communication mediators and inflammatory factors, and their impact on cellular function.Results: POLG and MAP2K7 were identified as common hub genes, with low expression observed across AA, MDS, and AML. There were distinct immune differentials among these diseases, with an enhanced correlation between immune cells and hub genes as the disease progressed. Macrophage Migration Inhibitory Factor(MIF) emerged as a key mediator of cellular communication. We identified 20 regulatory pathways of immune cells and inflammatory factors across different disease stages. In vitro validation confirmed low expression of the hub genes, which were inversely correlated with MIF and inflammatory factors, though they showed no significant impact on cell proliferation or migration.Conclusions: POLG and MAP2K7 demonstrate crucial roles in the progression from AA to MDS and, ultimately, to AML. These genes regulate more than 20 immune regulatory pathways through MIF-mediated communication, thereby influencing disease progression.
Keywords: aplastic anemia1, Myelodysplastic syndromes2, acute myeloid leukemia3, hub gene4, Bioinformatics5, Mendelian randomization6, plasmid7
Received: 18 Dec 2024; Accepted: 16 Apr 2025.
Copyright: © 2025 Shan, Xu, Yang, Sui, Sun, Zhuo and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Shiguo Liu, The Affiliated Hospital of Qingdao University, Qingdao, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
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