Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Acute and persistent symptoms in non-hospitalized PCR-confirmed COVID-19 patients

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. The Thioredoxin-Interacting Protein TXNIP Is a Putative Tumour Suppressor in Cutaneous T-Cell Lymphoma

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftCancer Research
Vol/bind80
Udgave nummer12
Sider (fra-til)2441-2450
Antal sider10
ISSN0008-5472
DOI
StatusUdgivet - 15 jun. 2020

Bibliografisk note

©2020 American Association for Cancer Research.

ID: 62032778