揭示厄德海姆-切斯特病的分子景观:来自甲基组和转录组整合的新见解

IF 13.4 1区 医学 Q1 HEMATOLOGY
Miriam Cerván-Martín, Francesco Pegoraro, Javier Martínez-López, Inmaculada Rodriguez-Martin, Ana Márquez, Lourdes Ortiz-Fernández, Marialbert Acosta-Herrera, Martin Kerick, Eduardo Andrés-León, Francesco Catamerò, Matthias Papo, Fleur Cohen-Aubart, Zahir Amoura, Julien Haroche, Augusto Vaglio, Javier Martín
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引用次数: 0

摘要

埃尔德海姆-切斯特病(ECD)是一种罕见的组织细胞增多症,具有广泛的临床表现。尽管体细胞突变与ECD有关,但其病因仍知之甚少。本研究旨在通过首次整合甲基组和转录组分析来确定参与ECD的新分子机制。收集了137例ECD患者和410例对照者的外周血样本。进行了全基因组DNA甲基化和转录组分析,随后使用不同的在线生物信息学工具进行了功能硅片研究。随后,整合了甲基组和转录组数据,并采用了药物再利用方法。我们的研究结果揭示了与ECD相关的2511个差异甲基化位点和1484个差异表达基因。综合分析确定了ECD患者DNA甲基化模式的46个改变,这些改变调节了29个改变基因的表达水平,突出了参与免疫反应和肿瘤发生的关键基因。值得注意的是,我们的研究结果确定了B细胞和NF-kB信号通路是ECD发病机制的新贡献者。最后,药物再利用分析确定了ECD患者的潜在治疗方案。总之,本研究在理解ECD的分子基础方面取得了重要进展,提出了参与ECD发病机制的新细胞类型和途径,并为临床治疗提供了新的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Unraveling the molecular landscape of Erdheim–Chester disease: new insights from methylome and transcriptome integration

Unraveling the molecular landscape of Erdheim–Chester disease: new insights from methylome and transcriptome integration

Erdheim–Chester Disease (ECD) is a rare histiocytosis characterized by a wide spectrum of clinical manifestations. Although somatic mutations have been involved in ECD, its etiology remains poorly understood. This study aimed to identify novel molecular mechanisms involved in ECD through the first integrated methylome and transcriptome analysis. Peripheral blood samples were collected from 137 ECD patients and 410 controls. Genome-wide DNA methylation and transcriptome analyses were performed, followed by functional in silico studies using different online bioinformatics tools. Subsequently, methylome and transcriptome data were integrated, and a drug repurposing approach was undertaken. Our results revealed 2511 differentially methylated positions and 1484 differentially expressed genes associated with ECD. The integrative analysis identified 46 alterations in DNA methylation patterns that regulate the expression levels of 29 altered genes in ECD patients, highlighting key genes involved in immune response and tumorigenesis. Remarkably, our results identified B cells and NF-kB signaling pathway as novel contributors of ECD pathogenesis. Finally, the drug repurposing analysis identified potential therapeutic options for ECD patients. In conclusion, this study represents an important advance in understanding the molecular basis of ECD, proposing novel cell types and pathways involved in ECD pathogenesis and suggesting new avenues for clinical management.

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来源期刊
Leukemia
Leukemia 医学-血液学
CiteScore
18.10
自引率
3.50%
发文量
270
审稿时长
3-6 weeks
期刊介绍: Title: Leukemia Journal Overview: Publishes high-quality, peer-reviewed research Covers all aspects of research and treatment of leukemia and allied diseases Includes studies of normal hemopoiesis due to comparative relevance Topics of Interest: Oncogenes Growth factors Stem cells Leukemia genomics Cell cycle Signal transduction Molecular targets for therapy And more Content Types: Original research articles Reviews Letters Correspondence Comments elaborating on significant advances and covering topical issues
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