PRMT1 facilitates the tumorigenesis of chronic lymphocytic leukemia by regulating methylation of MAST1
Menée à l'aide de lignées cellulaires, de modèles murins et d'échantillons sanguins prélevés sur des patients atteints d'une leucémie lymphoïde chronique, cette étude met en évidence un mécanisme par lequel la méthyltransférase PRMT1 favorise la tumorigenèse en régulant la méthylation de la kinase MAST1
Protein arginine methyltransferase 1 (PRMT1) serves as a crucial regulator of post-translational modifications of proteins. While PRMT1 has been implicated in the progression of various cancers, its specific role in chronic lymphocytic leukemia (CLL) remains to be fully elucidated. This study aimed to investigate the oncogenic function of PRMT1 and assess the therapeutic efficacy of a selective PRMT1 inhibitor, C7280948, in CLL. Elevated expression of PRMT1 was observed in CLL cells and was associated with unfavorable prognosis. Additionally, in vitro and in vivo experiments demonstrated that treatment with C7280948 effectively inhibited tumor growth in CLL. Quantitative proteomics and co-immunoprecipitation analyses revealed an interaction between PRMT1 and MAST1, which was found to facilitate CLL progression. PRMT1 inhibition decreased the asymmetric dimethylarginine of MAST1 at R806 and downregulated the activation of the MAPK pathway by affecting the phosphorylation of MEK1 and ERK1/2 in CLL cells. In summary, our results indicated that PRMT1 promoted CLL tumorigenesis via MAST1-mediated regulation of MEK1 signaling and highlighted the potential of C7280948 as a novel therapeutic agent for CLL treatment.
Leukemia , article en libre accès, 2026