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

ABSTRACT:

Simple Summary

Approximately 15–25% of acute lymphoblastic leukemias (ALL) originate from T-lineage cells. The prognosis of T-ALL is less favorable than in B-ALL and patients experience more often relapse, which is associated with dismal survival. No established prognostic biomarkers exist for T-ALL. Here, we identified the high expression of PRMT7 in T-ALL cells. Genetic deletion of PRMT7 decreased the colony formation of T-ALL cells and altered arginine monomethylation patterns in protein complexes associated with RNA and DNA processing. Moreover, several proteins with an established role in the pathogenesis of T-ALL had disrupted arginine monomethylation patterns. Among them was RUNX1, whose target gene expression was consequently deregulated.

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.

SUBMITTER: Oksa L

PROVIDER: S-EPMC9101393 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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