Protein arginine methyltransferase 2 controls inflammatory signaling in acute myeloid leukemia.
Fiche publication
Date publication
juin 2024
Journal
Communications biology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BASTIE Jean-Noël, Dr DELVA Laurent, Dr HERAULT Yann, Pr MAYNADIE Marc, Pr CALLANAN Mary, Dr AUCAGNE Romain, Dr GUIDEZ Fabien
Tous les auteurs :
Sauter C, Morin T, Guidez F, Simonet J, Fournier C, Row C, Masnikov D, Pernon B, Largeot A, Aznague A, Hérault Y, Sauvageau G, Maynadié M, Callanan M, Bastie JN, Aucagne R, Delva L
Lien Pubmed
Résumé
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.
Mots clés
Protein-Arginine N-Methyltransferases, metabolism, Leukemia, Myeloid, Acute, genetics, Animals, Humans, Signal Transduction, Mice, Inflammation, metabolism, Mice, Knockout, NF-kappa B, metabolism, Cell Line, Tumor, STAT3 Transcription Factor, metabolism, Female, Male, Mice, Inbred C57BL, Intracellular Signaling Peptides and Proteins
Référence
Commun Biol. 2024 06 20;7(1):753