Arginine Methyltransferase PRMT7 Deregulates Expression of RUNX1 Target Genes in T-Cell Acute Lymphoblastic Leukemia

Cancers

Masafumi Seki¹  Junko Takita²  Laura Oksa³  Saara Laukkanen³  Artturi Mäkinen³  Noora Hyvärinen³  Atte Nikkilä³  Olli Lohi³  Merja Heinäniemi⁴  Otto Kauko⁵  Anne Rokka⁵  Pekka Haapaniemi⁵ 

[1] Department of Cell and Molecular Biology, Karolinska Institutet, SE-17165 Solna, Sweden;Graduate School of Medicine, Kyoto University, Kyoto JP-606-8501, Japan;Tampere Center for Child, Adolescent, and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, FI-33520 Tampere, Finland;The Institute of Biomedicine, University of Eastern Finland, FI-70211 Kuopio, Finland;Turku Bioscience Center, University of Turku and Åbo Akademi University, FI-20014 Turku, Finland;

关键词: Leukemia;    T-ALL;    arginine methylation;    PRMT7;    RUNX1;   

DOI  :  10.3390/cancers14092169

来源: DOAJ

【 摘 要 】

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with no well-established prognostic biomarkers. We examined the expression of protein arginine methyltransferases across hematological malignancies and discovered high levels of PRMT7 mRNA in T-ALL, particularly in the mature subtypes of T-ALL. The genetic deletion of PRMT7 by CRISPR-Cas9 reduced the colony formation of T-ALL cells and changed arginine monomethylation patterns in protein complexes associated with the RNA and DNA processing and the T-ALL pathogenesis. Among them was RUNX1, whose target gene expression was consequently deregulated. These results suggest that PRMT7 plays an active role in the pathogenesis of T-ALL.

【 授权许可】

Unknown