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
{"title":"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","authors":"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","doi":"10.1038/s41375-025-02742-z","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"36 1","pages":""},"PeriodicalIF":13.4000,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Unraveling the molecular landscape of Erdheim–Chester disease: new insights from methylome and transcriptome integration\",\"authors\":\"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\",\"doi\":\"10.1038/s41375-025-02742-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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.</p>\",\"PeriodicalId\":18109,\"journal\":{\"name\":\"Leukemia\",\"volume\":\"36 1\",\"pages\":\"\"},\"PeriodicalIF\":13.4000,\"publicationDate\":\"2025-08-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Leukemia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41375-025-02742-z\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Leukemia","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41375-025-02742-z","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
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.
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