STAT3 activation in large granular lymphocyte leukemia is associated with cytokine signaling and DNA hypermethylation.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
12
02
2021
accepted:
05
05
2021
revised:
04
05
2021
pubmed:
3
6
2021
medline:
30
12
2021
entrez:
2
6
2021
Statut:
ppublish
Résumé
Large granular lymphocyte leukemia (LGLL) is characterized by somatic gain-of-function STAT3 mutations. However, the functional effects of STAT3 mutations on primary LGLL cells have not been studied in detail. In this study, we show that CD8+ T cells isolated from STAT3 mutated LGLL patients have high protein levels of epigenetic regulators, such as DNMT1, and are characterized by global hypermethylation. Correspondingly, treatment of healthy CD8+ T cells with IL-6, IL-15, and/or MCP-1 cytokines resulted in STAT3 activation, increased DNMT1, EZH2, c-MYC, l-MYC, MAX, and NFκB levels, increased DNA methylation, and increased oxidative stress. Similar results were discovered in KAI3 NK cells overexpressing gain-of-function STAT3
Identifiants
pubmed: 34075200
doi: 10.1038/s41375-021-01296-0
pii: 10.1038/s41375-021-01296-0
pmc: PMC8632689
doi:
Substances chimiques
Biomarkers, Tumor
0
Cytokines
0
STAT3 Transcription Factor
0
STAT3 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3430-3443Informations de copyright
© 2021. The Author(s).
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