دورية أكاديمية
Multiomics analysis of IgM monoclonal gammopathies reveals epigenetic influence on oncogenesis via DNA methylation.
| العنوان: | Multiomics analysis of IgM monoclonal gammopathies reveals epigenetic influence on oncogenesis via DNA methylation. |
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| المؤلفون: | Chohan K; Department of Medicine, Mayo Clinic, Rochester, MN., Paludo J; Division of Hematology, Mayo Clinic, Rochester, MN., Dasari S; Department of Health Sciences Research, Mayo Clinic, Rochester, MN., Mondello P; Division of Hematology, Mayo Clinic, Rochester, MN., Novak JP; Division of Hematology, Mayo Clinic, Rochester, MN., Abeykoon JP; Division of Hematology, Mayo Clinic, Rochester, MN., Wenzl K; Division of Hematology, Mayo Clinic, Rochester, MN., Yang ZZ; Division of Hematology, Mayo Clinic, Rochester, MN., Jalali S; Division of Hematology, Mayo Clinic, Rochester, MN., Bhardwaj V; Division of Hematology, Mayo Clinic, Rochester, MN., Krull JE; Division of Hematology, Mayo Clinic, Rochester, MN., Braggio E; Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, AZ., Manske MK; Division of Hematology, Mayo Clinic, Rochester, MN., Paulus A; Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL., Reeder CB; Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, AZ., Ailawadhi S; Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL., Chanan-Khan A; Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL., Kapoor P; Division of Hematology, Mayo Clinic, Rochester, MN., Kyle RA; Division of Hematology, Mayo Clinic, Rochester, MN., Gertz MA; Division of Hematology, Mayo Clinic, Rochester, MN., Novak AJ; Division of Hematology, Mayo Clinic, Rochester, MN., Ansell SM; Division of Hematology, Mayo Clinic, Rochester, MN. |
| المصدر: | Blood [Blood] 2024 Sep 19; Vol. 144 (12), pp. 1284-1289. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print Cited Medium: Internet ISSN: 1528-0020 (Electronic) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York] : Elsevier Original Publication: New York, Grune & Stratton [etc.] |
| مواضيع طبية MeSH: | DNA Methylation* , Epigenesis, Genetic* , Immunoglobulin M*/genetics , Waldenstrom Macroglobulinemia*/genetics , Waldenstrom Macroglobulinemia*/immunology , Monoclonal Gammopathy of Undetermined Significance*/genetics , Monoclonal Gammopathy of Undetermined Significance*/pathology , Monoclonal Gammopathy of Undetermined Significance*/metabolism, Humans ; Male ; Female ; Aged ; Middle Aged ; Carcinogenesis/genetics ; Paraproteinemias/genetics ; Receptors, CXCR4/genetics ; Receptors, CXCR4/metabolism ; Prospective Studies ; Signal Transduction/genetics ; Multiomics |
| مستخلص: | Abstract: Currently, the role of DNA methylation in the immunoglobulin M (IgM) monoclonal gammopathy disease spectrum remains poorly understood. In the present study, a multiomics prospective analysis was conducted integrating DNA methylation, RNA sequencing (RNA-seq), and whole-exome sequencing data in 34 subjects (23 with Waldenström macroglobulinemia [WM], 6 with IgM monoclonal gammopathy of undetermined significance [MGUS], and 5 normal controls). Analysis was focused on defining differences between IgM gammopathies (WM/IgM-MGUS) compared with controls, and specifically between WM and IgM-MGUS. Between groups, genome-wide DNA methylation analysis demonstrated a significant number of differentially methylated regions that were annotated according to genomic region. Next, integration of RNA-seq data was performed to identify potentially epigenetically deregulated pathways. We found that pathways involved in cell cycle, metabolism, cytokine/immune signaling, cytoskeleton, tumor microenvironment, and intracellular signaling were differentially activated and potentially epigenetically regulated. Importantly, there was a positive enrichment of the CXCR4 signaling pathway along with several interleukin (interleukin 6 [IL-6], IL-8, and IL-15) signaling pathways in WM compared with IgM-MGUS. Further assessment of known tumor suppressor genes and oncogenes uncovered differential promoter methylation of several targets with concordant change in gene expression, including CCND1 and CD79B. Overall, this report defines how aberrant DNA methylation in IgM gammopathies may play a critical role in the epigenetic control of oncogenesis and key cellular functions. (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.) |
| المشرفين على المادة: | 0 (Immunoglobulin M) 0 (Receptors, CXCR4) |
| تواريخ الأحداث: | Date Created: 20240705 Date Completed: 20240919 Latest Revision: 20240919 |
| رمز التحديث: | 20240923 |
| DOI: | 10.1182/blood.2023023639 |
| PMID: | 38968152 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1528-0020 |
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| DOI: | 10.1182/blood.2023023639 |