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

Laura Oksa; Artturi Mäkinen; Atte Nikkilä; Noora Hyvärinen; Saara Laukkanen; Anne Rokka; Pekka Haapaniemi; Masafumi Seki; Junko Takita; Otto Kauko; Merja Heinäniemi; Olli Lohi

doi:10.3390/cancers14092169

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

Cancers (Basel). 2022 Apr 26;14(9):2169. doi: 10.3390/cancers14092169.

Authors

Laura Oksa¹, Artturi Mäkinen^{1

2}, Atte Nikkilä¹, Noora Hyvärinen¹, Saara Laukkanen¹, Anne Rokka³, Pekka Haapaniemi³, Masafumi Seki⁴, Junko Takita⁵, Otto Kauko³, Merja Heinäniemi⁶, Olli Lohi^{1

7}

Affiliations

¹ Tampere Center for Child, Adolescent, and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, FI-33520 Tampere, Finland.
² Fimlab Laboratories, Department of Pathology, Tampere University Hospital, FI-33520 Tampere, Finland.
³ Turku Bioscience Center, University of Turku and Åbo Akademi University, FI-20014 Turku, Finland.
⁴ Department of Cell and Molecular Biology, Karolinska Institutet, SE-17165 Solna, Sweden.
⁵ Graduate School of Medicine, Kyoto University, Kyoto JP-606-8501, Japan.
⁶ The Institute of Biomedicine, University of Eastern Finland, FI-70211 Kuopio, Finland.
⁷ Tays Cancer Center, Tampere University Hospital, FI-33520 Tampere, Finland.

Abstract

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.

Keywords: Leukemia; PRMT7; RUNX1; T-ALL; arginine methylation.