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Protein arginine methyltransferase 2 controls inflammatory signaling in acute myeloid leukemia

Protein arginine methyltransferase 2 controls inflammatory signaling in acute myeloid leukemia

Authors :
Camille Sauter
Thomas Morin
Fabien Guidez
John Simonet
Cyril Fournier
Céline Row
Denis Masnikov
Baptiste Pernon
Anne Largeot
Aziza Aznague
Yann Hérault
Guy Sauvageau
Marc Maynadié
Mary Callanan
Jean-Noël Bastie
Romain Aucagne
Laurent Delva
Source :
Communications Biology, Vol 7, Iss 1, Pp 1-12 (2024)
Publication Year :
2024
Publisher :
Nature Portfolio, 2024.

Abstract

Abstract Arginine methylation is catalyzed by protein arginine methyltransferases (PRMTs) and is involved in various cellular processes, including cancer development. PRMT2 expression is increased in several cancer types although its role in acute myeloid leukemia (AML) remains unknown. Here, we investigate the role of PRMT2 in a cohort of patients with AML, PRMT2 knockout AML cell lines as well as a Prmt2 knockout mouse model. In patients, low PRMT2 expressors are enriched for inflammatory signatures, including the NF-κB pathway, and show inferior survival. In keeping with a role for PRMT2 in control of inflammatory signaling, bone marrow-derived macrophages from Prmt2 KO mice display increased pro-inflammatory cytokine signaling upon LPS treatment. In PRMT2-depleted AML cell lines, aberrant inflammatory signaling has been linked to overproduction of IL6, resulting from a deregulation of the NF-κB signaling pathway, therefore leading to hyperactivation of STAT3. Together, these findings identify PRMT2 as a key regulator of inflammation in AML.

Subjects

Subjects :
Biology (General)
QH301-705.5

Details

Language :
English
ISSN :
23993642 and 46318658
Volume :
7
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Communications Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.967c7436105d4631865893350841f114
Document Type :
article
Full Text :
https://doi.org/10.1038/s42003-024-06453-6