Targeting RIOK2 ATPase activity leads to decreased protein synthesis and cell death in acute myeloid leukemia

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Standard

Targeting RIOK2 ATPase activity leads to decreased protein synthesis and cell death in acute myeloid leukemia. / Messling, Jan-Erik; Agger, Karl; Andersen, Kasper L; Kromer, Kristina; Kuepper, Hanna Maria; Lund, Anders H; Helin, Kristian.

I: Blood, Bind 139, Nr. 2, 2022, s. 245-255.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Messling, J-E, Agger, K, Andersen, KL, Kromer, K, Kuepper, HM, Lund, AH & Helin, K 2022, 'Targeting RIOK2 ATPase activity leads to decreased protein synthesis and cell death in acute myeloid leukemia', Blood, bind 139, nr. 2, s. 245-255. https://doi.org/10.1182/blood.2021012629

APA

Messling, J-E., Agger, K., Andersen, K. L., Kromer, K., Kuepper, H. M., Lund, A. H., & Helin, K. (2022). Targeting RIOK2 ATPase activity leads to decreased protein synthesis and cell death in acute myeloid leukemia. Blood, 139(2), 245-255. https://doi.org/10.1182/blood.2021012629

Vancouver

Messling J-E, Agger K, Andersen KL, Kromer K, Kuepper HM, Lund AH o.a. Targeting RIOK2 ATPase activity leads to decreased protein synthesis and cell death in acute myeloid leukemia. Blood. 2022;139(2):245-255. https://doi.org/10.1182/blood.2021012629

Author

Messling, Jan-Erik ; Agger, Karl ; Andersen, Kasper L ; Kromer, Kristina ; Kuepper, Hanna Maria ; Lund, Anders H ; Helin, Kristian. / Targeting RIOK2 ATPase activity leads to decreased protein synthesis and cell death in acute myeloid leukemia. I: Blood. 2022 ; Bind 139, Nr. 2. s. 245-255.

Bibtex

@article{6434e80d78014683a7cba56d2740c75a,

title = "Targeting RIOK2 ATPase activity leads to decreased protein synthesis and cell death in acute myeloid leukemia",

abstract = "Novel therapies for the treatment of acute myeloid leukemia (AML) are urgently needed as current treatments do not cure the majority of AML patients. Here, we report on a domain-focused, kinome-wide CRISPR-Cas9 screen to identify protein kinase targets for the treatment of AML, which led to the identification of Rio-kinase 2 (RIOK2) as a potential novel target. We show that loss of RIOK2 leads to a decrease in protein synthesis and to ribosomal instability followed by apoptosis in leukemic cells, but not in fibroblasts. Moreover, we demonstrate that the ATPase function of RIOK2 is required for cell survival. By using a small molecule inhibitor, we show that pharmacological inhibition of RIOK2 similarly leads to loss of protein synthesis and apoptosis and affects leukemic cell growth in vivo. Our results provide proof-of-concept for targeting RIOK2 as a potential treatment for AML patients.",

author = "Jan-Erik Messling and Karl Agger and Andersen, {Kasper L} and Kristina Kromer and Kuepper, {Hanna Maria} and Lund, {Anders H} and Kristian Helin",

note = "Copyright {\textcopyright} 2021 American Society of Hematology.",

year = "2022",

doi = "10.1182/blood.2021012629",

language = "English",

volume = "139",

pages = "245--255",

journal = "Blood",

issn = "0006-4971",

publisher = "American Society of Hematology",

number = "2",

}

RIS

TY - JOUR

T1 - Targeting RIOK2 ATPase activity leads to decreased protein synthesis and cell death in acute myeloid leukemia

AU - Messling, Jan-Erik

AU - Agger, Karl

AU - Andersen, Kasper L

AU - Kromer, Kristina

AU - Kuepper, Hanna Maria

AU - Lund, Anders H

AU - Helin, Kristian

PY - 2022

Y1 - 2022

N2 - Novel therapies for the treatment of acute myeloid leukemia (AML) are urgently needed as current treatments do not cure the majority of AML patients. Here, we report on a domain-focused, kinome-wide CRISPR-Cas9 screen to identify protein kinase targets for the treatment of AML, which led to the identification of Rio-kinase 2 (RIOK2) as a potential novel target. We show that loss of RIOK2 leads to a decrease in protein synthesis and to ribosomal instability followed by apoptosis in leukemic cells, but not in fibroblasts. Moreover, we demonstrate that the ATPase function of RIOK2 is required for cell survival. By using a small molecule inhibitor, we show that pharmacological inhibition of RIOK2 similarly leads to loss of protein synthesis and apoptosis and affects leukemic cell growth in vivo. Our results provide proof-of-concept for targeting RIOK2 as a potential treatment for AML patients.

AB - Novel therapies for the treatment of acute myeloid leukemia (AML) are urgently needed as current treatments do not cure the majority of AML patients. Here, we report on a domain-focused, kinome-wide CRISPR-Cas9 screen to identify protein kinase targets for the treatment of AML, which led to the identification of Rio-kinase 2 (RIOK2) as a potential novel target. We show that loss of RIOK2 leads to a decrease in protein synthesis and to ribosomal instability followed by apoptosis in leukemic cells, but not in fibroblasts. Moreover, we demonstrate that the ATPase function of RIOK2 is required for cell survival. By using a small molecule inhibitor, we show that pharmacological inhibition of RIOK2 similarly leads to loss of protein synthesis and apoptosis and affects leukemic cell growth in vivo. Our results provide proof-of-concept for targeting RIOK2 as a potential treatment for AML patients.

U2 - 10.1182/blood.2021012629

DO - 10.1182/blood.2021012629

M3 - Journal article

C2 - 34359076

VL - 139

SP - 245

EP - 255

JO - Blood

JF - Blood

SN - 0006-4971

IS - 2

ER -

ID: 275607578