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

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

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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.

Original language	English
Article number	2169
Number of pages	18
Journal	Cancers
Volume	14
Issue number	9
DOIs	https://doi.org/10.3390/cancers14092169
Publication status	Published - 2022
Publication type	A1 Journal article-refereed

Funding

Funding: This work was supported by grants from the Academy of Finland (O.L. and M.H. 321553, O.L., 310106 and 341540), Cancer Foundation Finland (O.L., M.H), Jane and Aatos Erkko Foundation (O.L., M.H.), Sigrid Juselius Foundation (O.L., M.H.), Finnish Hematology Association (L.O.), and the Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital (O.L. 9V033 and 9X027). Acknowledgments: The authors acknowledge the Tampere facility of Flow Cytometry, Tampere facility of iPS Cells, Tampere Imaging Facility and the Biocenter Finland (BF) for their services. Jan Cools and Charles de Bock are acknowledged for providing the Jurkat Cas9 cells and px321-GFP - plasmids for CRISPR studies. Mass spectrometry analysis was performed at the Turku Proteomics Facility, University of Turku and Åbo Akademi University. The facility is supported by Biocenter Finland. Part of the work was carried out with the support of UEF Bioinformatics Center, University of Eastern Finland, Finland. We wish to thank Jorma Kulmala, Eini Eskola, and Gitte Gaethofs for assistance in laboratory work.

Keywords

arginine methylation
leukemia
PRMT7
RUNX1
T-ALL

Publication forum classification

Publication forum level 1

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cancers14092169Licence: CC BY

cancers-14-02169-v2Final published version, 2.83 MBLicence: CC BY

https://urn.fi/URN:NBN:fi:tuni-202205094541Licence: CC BY

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@article{a18d9d6278c44c2584e56cece81d28ae,

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

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 = "arginine methylation, leukemia, PRMT7, RUNX1, T-ALL",

author = "Laura Oksa and Artturi M{\"a}kinen and Atte Nikkil{\"a} and Noora Hyv{\"a}rinen and Saara Laukkanen and Anne Rokka and Pekka Haapaniemi and Masafumi Seki and Junko Takita and Otto Kauko and Merja Hein{\"a}niemi and Olli Lohi",

note = "Funding Information: Funding: This work was supported by grants from the Academy of Finland (O.L. and M.H. 321553, O.L., 310106 and 341540), Cancer Foundation Finland (O.L., M.H), Jane and Aatos Erkko Foundation (O.L., M.H.), Sigrid Juselius Foundation (O.L., M.H.), Finnish Hematology Association (L.O.), and the Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital (O.L. 9V033 and 9X027). Funding Information: Acknowledgments: The authors acknowledge the Tampere facility of Flow Cytometry, Tampere facility of iPS Cells, Tampere Imaging Facility and the Biocenter Finland (BF) for their services. Jan Cools and Charles de Bock are acknowledged for providing the Jurkat Cas9 cells and px321-GFP - plasmids for CRISPR studies. Mass spectrometry analysis was performed at the Turku Proteomics Facility, University of Turku and {\AA}bo Akademi University. The facility is supported by Biocenter Finland. Part of the work was carried out with the support of UEF Bioinformatics Center, University of Eastern Finland, Finland. We wish to thank Jorma Kulmala, Eini Eskola, and Gitte Gaethofs for assistance in laboratory work. Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

doi = "10.3390/cancers14092169",

language = "English",

volume = "14",

number = "9",

}

TY - JOUR

T1 - Arginine Methyltransferase PRMT7 Deregulates Expression of RUNX1 Target Genes in T-Cell Acute Lymphoblastic Leukemia

AU - Oksa, Laura

AU - Mäkinen, Artturi

AU - Nikkilä, Atte

AU - Hyvärinen, Noora

AU - Laukkanen, Saara

AU - Rokka, Anne

AU - Haapaniemi, Pekka

AU - Seki, Masafumi

AU - Takita, Junko

AU - Kauko, Otto

AU - Heinäniemi, Merja

AU - Lohi, Olli

N1 - Funding Information: Funding: This work was supported by grants from the Academy of Finland (O.L. and M.H. 321553, O.L., 310106 and 341540), Cancer Foundation Finland (O.L., M.H), Jane and Aatos Erkko Foundation (O.L., M.H.), Sigrid Juselius Foundation (O.L., M.H.), Finnish Hematology Association (L.O.), and the Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital (O.L. 9V033 and 9X027). Funding Information: Acknowledgments: The authors acknowledge the Tampere facility of Flow Cytometry, Tampere facility of iPS Cells, Tampere Imaging Facility and the Biocenter Finland (BF) for their services. Jan Cools and Charles de Bock are acknowledged for providing the Jurkat Cas9 cells and px321-GFP - plasmids for CRISPR studies. Mass spectrometry analysis was performed at the Turku Proteomics Facility, University of Turku and Åbo Akademi University. The facility is supported by Biocenter Finland. Part of the work was carried out with the support of UEF Bioinformatics Center, University of Eastern Finland, Finland. We wish to thank Jorma Kulmala, Eini Eskola, and Gitte Gaethofs for assistance in laboratory work. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - arginine methylation

KW - leukemia

KW - PRMT7

KW - RUNX1

KW - T-ALL

U2 - 10.3390/cancers14092169

DO - 10.3390/cancers14092169

M3 - Article

AN - SCOPUS:85128780353

SN - 2072-6694

VL - 14

JO - Cancers

JF - Cancers

IS - 9

M1 - 2169

ER -

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

Abstract

Funding

Keywords

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ASJC Scopus subject areas

UN SDGs

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