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

精氨酸甲基转移酶 PRMT7 解除 T 细胞急性淋巴细胞白血病中 RUNX1 靶基因的表达

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

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.

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