Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Activation of a Subset of Evolutionarily Young Transposable Elements and Innate Immunity Are Linked to Clinical Responses to 5-Azacytidine

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Transcriptome-Wide Association Study Identifies New Candidate Susceptibility Genes for Glioma

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. A large-cohort, longitudinal study determines pre-cancer disease routes across different cancer types

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Genetic data from nearly 63,000 women of European descent predicts DNA methylation biomarkers and epithelial ovarian cancer risk

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Risk of new malignancies among patients with CLL treated with chemotherapy: results of a Danish population-based study

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Protein phosphatase, Mg2+/Mn2+-dependent 1D (PPM1D) mutations in haematological cancer

    Research output: Contribution to journalReviewpeer-review

  3. Genome-Wide Circular RNA Expression Patterns Reflect Resistance to Immunomodulatory Drugs in Multiple Myeloma Cells

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Detailed Long-Term Follow-Up of Patients Who Relapsed After the Nordic Mantle Cell Lymphoma Trials: MCL2 and MCL3

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

The DNA methyltransferase inhibitors (DNMTi) 5-azacytidine and 5-aza-2-deoxycytidine have been approved for the treatment of different types of hematologic malignancies. However, only about 50% of patients respond to treatment. Therefore, a more comprehensive understanding of the molecular changes in patients treated with DNMTi is needed. Here, we examined gene expression profiles in a total of 150 RNA samples from two adult cohorts and one pediatric cohort with hematologic cancers taken before, during, and after treatment with 5-azacytidine (40 patients; 15 nonresponders, 25 responders). Using each patient as their own control, malignant cells showed preferential activation of a subset of evolutionarily young transposable elements (TE), including endogenous retroviral long terminal repeats (LTR), short and long interspersed nuclear elements (SINE and LINE), and the type I IFN pathway in responders, all independent of disease classification. Transfection of eight upregulated LTRs into recipient human cells in culture showed robust and heterogenous activation of six genes in the type I IFN pathway. These results, obtained in diverse hematologic disease entities, show that common targets (TE) activated by the same drug (5-azacytidine) elicit an immune response, which may be important for patient's responses to DNMTi. SIGNIFICANCE: Activation of specific classes of evolutionarily young transposable elements can lead to activation of the innate immune system.

Original languageEnglish
JournalCancer Research
Volume80
Issue number12
Pages (from-to)2441-2450
Number of pages10
ISSN0008-5472
DOIs
Publication statusPublished - 15 Jun 2020

    Research areas

  • Aged, Aged, 80 and over, Antimetabolites, Antineoplastic/pharmacology, Azacitidine/pharmacology, Cohort Studies, DNA Transposable Elements/drug effects, Drug Resistance, Neoplasm/genetics, Endogenous Retroviruses/genetics, Female, Gene Expression Regulation, Neoplastic/drug effects, Hematologic Neoplasms/drug therapy, Humans, Immunity, Innate/drug effects, Interferon Type I/metabolism, Male, Middle Aged, Molecular Mimicry/immunology, RNA-Seq, Signal Transduction/drug effects, Up-Regulation/drug effects

ID: 62032778