Protein arginine methyltransferase 2 controls inflammatory signaling in acute myeloid leukemia

• Published in: Communications biology Vol. 7; no. 1; pp. 753 - 12
• Main Authors: Sauter, Camille, Morin, Thomas, Guidez, Fabien, Simonet, John, Fournier, Cyril, Row, Céline, Masnikov, Denis, Pernon, Baptiste, Largeot, Anne, Aznague, Aziza, Hérault, Yann, Sauvageau, Guy, Maynadié, Marc, Callanan, Mary, Bastie, Jean-Noël, Aucagne, Romain, Delva, Laurent
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.06.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13/109; 13/31; 38/39; 38/91; 42/41; 631/67/1990/283/1897; 64/110; 64/60; 692/4028/67/1990/283/1897; 82/29; Acute myeloid leukemia; Animals; Arginine; Biomedical and Life Sciences; Bone marrow; Cell Line, Tumor; Female; Humans; Inflammation; Inflammation - genetics; Inflammation - metabolism; Intracellular Signaling Peptides and Proteins; Leukemia; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - metabolism; Leukemia, Myeloid, Acute - pathology; Life Sciences; Macrophages; Male; Methylation; Mice; Mice, Inbred C57BL; Mice, Knockout; NF-kappa B - metabolism; NF-κB protein; Protein arginine methyltransferase; Protein-Arginine N-Methyltransferases - genetics; Protein-Arginine N-Methyltransferases - metabolism; Signal Transduction; Stat3 protein; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-024-06453-6

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. PRMT2 is a key regulator of inflammation in acute myeloid leukemia. PRMT2-deficient cells exhibit a pro-inflammatory profile associated with STAT3 activation.