TY - JOUR
T1 - Protein arginine methyltransferase 2 controls inflammatory signaling in acute myeloid leukemia
AU - Sauter, Camille
AU - Morin, Thomas
AU - Guidez, Fabien
AU - Simonet, John
AU - Fournier, Cyril
AU - Row, Céline
AU - Masnikov, Denis
AU - Pernon, Baptiste
AU - Largeot, Anne
AU - Aznague, Aziza
AU - Hérault, Yann
AU - Sauvageau, Guy
AU - Maynadié, Marc
AU - Callanan, Mary
AU - Bastie, Jean Noël
AU - Aucagne, Romain
AU - Delva, Laurent
N1 - Acknowledgements
We gratefully acknowledge the IMAFLOW Core Facility at the Université de Bourgogne supported by Burgundy Regional Council (Anabelle Sequeira, Serge Monier, and Nicolas Pernet) for all the flow cytometry data acquisition and helpful advice on data analyzes, and the animal facility (Valérie Saint-Giorgio) from the Université de Bourgogne for the mouse studies. We also thank Dr François Hermetet for providing the antibodies against phosphorylated and total MAPK proteins. This work was supported by a French Government grant managed by the French National Research Agency (ANR) under the program “Investissements d’Avenir” with reference ANR-11 LABX-0021 (LipSTIC LabEx), the Association Laurette Fugain (to Laurent Delva), the Ligue Nationale contre le Cancer (Coordination Interrégionale des régions Grand Est et Bourgogne Franche Comté) (to Laurent Delva), the Cancéropôle Est (to Laurent Delva), the FEDER, and the Regional Council of Bourgogne Franche Comté. Camille Sauter was supported by fellowships from the Fondation pour la Recherche Médicale (FRM) (ECO201906009006; 3 years), the Fondation ARC (ARCDOC42022010004491; 1 year) and the Société Française d’Hématologie (SFH; 4 months), John Simonet by the LipSTIC LabEx, Denis Masnikov and Baptiste Pernon by the French Ministère de l’Enseignement Supérieur, de la Recherche et de l’Innovation (MESRI), and Dr. Anne Largeot by fellowships from Inserm associated with the Regional Council of Bourgogne and the SFH.
Publisher Copyright:
© The Author(s) 2024.
PY - 2024/6/20
Y1 - 2024/6/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85196388747&partnerID=8YFLogxK
U2 - 10.1038/s42003-024-06453-6
DO - 10.1038/s42003-024-06453-6
M3 - Article
C2 - 38902349
AN - SCOPUS:85196388747
SN - 2399-3642
VL - 7
SP - 753
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 753
ER -