Diagenode

Myelodysplastic Syndrome associated TET2 mutations affect NK cellfunction and genome methylation.


Boy M. et al.

Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders, representing high risk of progression to acute myeloid leukaemia, and frequently associated to somatic mutations, notably in the epigenetic regulator TET2. Natural Killer (NK) cells play a role in the anti-leukemic immune response via their cytolytic activity. Here we show that patients with MDS clones harbouring mutations in the TET2 gene are characterised by phenotypic defects in their circulating NK cells. Remarkably, NK cells and MDS clones from the same patient share the TET2 genotype, and the NK cells are characterised by increased methylation of genomic DNA and reduced expression of Killer Immunoglobulin-like receptors (KIR), perforin, and TNF-α. In vitro inhibition of TET2 in NK cells of healthy donors reduces their cytotoxicity, supporting its critical role in NK cell function. Conversely, NK cells from patients treated with azacytidine (#NCT02985190; https://clinicaltrials.gov/ ) show increased KIR and cytolytic protein expression, and IFN-γ production. Altogether, our findings show that, in addition to their oncogenic consequences in the myeloid cell subsets, TET2 mutations contribute to repressing NK-cell function in MDS patients.

Tags
Antibody
Premium RRBS Kit
DNA Methylation Profiling (RRBS Service)

Share this article

Published
February, 2023

Source

Products used in this publication

  • default alt
    G02020000
    RRBS受託サービス (Reduced Representation Bisulfite Se...
  • Methylation kit icon
    C02030036
    Premium RRBS kit V2
  • Methylation kit icon
    C02030037
    Premium RRBS kit V2 x96 RRBS for low DNA amoun...
  • Antibody ChIP icon
    C15410255-100
    TET2 polyclonal antibody
  • Mouse IgG
    C15410206
    Rabbit IgG

イベント

  • Long-Read Sequencing Meeting 2024
    Uppsala, Sweden
    Oct 21-Oct 23, 2024
  • NextGen Omics 2024
    London, UK
    Oct 23-Oct 25, 2024
  • FEBS 2024
    Budapest, Hungary
    Oct 28-Oct 31, 2024
  • 5th Danube Conference on Epigenetics
    Budapest, Hungary
    Oct 28-Oct 31, 2024
 すべてのイベントを見る

 


       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy