Protein Arginine Methyltransferase 2 Controls Inflammatory Signaling in Acute Myeloid Leukemia

Overview

Journal Commun Biol

Specialty Biology

Date 2024 Jun 20

PMID 38902349

Authors

Camille Sauter

Thomas Morin

Fabien Guidez

John Simonet

Cyril Fournier

Celine Row

Denis Masnikov

Baptiste Pernon

Anne Largeot

Aziza Aznague

Yann Herault

Guy Sauvageau

Marc Maynadie

Mary Callanan

Jean-Noel Bastie

Romain Aucagne

Laurent Delva

Affiliations

Soon will be listed here.

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.

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