Počet záznamů: 1
Ppm1d truncating mutations promote the development of genotoxic stress-induced AML
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SYSNO ASEP 0578776 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Ppm1d truncating mutations promote the development of genotoxic stress-induced AML Tvůrce(i) Burocziová, Monika (UMG-J)
Daněk, Petr (UMG-J)
Oravetzová, Anna (UMG-J)
Chalupová, Zuzana (UMG-J)
Alberich-Jorda, Meritxell (UMG-J) RID
Macůrek, Libor (UMG-J) RID, ORCIDCelkový počet autorů 6 Zdroj.dok. Leukemia. - : Springer - ISSN 0887-6924
Roč. 37, Sep (2023), s. 2209-2220Poč.str. 12 s. Jazyk dok. eng - angličtina Země vyd. DE - Německo Klíč. slova cell self-renewal ; stem-cell ; phosphatase wip1 ; p53 ; cycle ; hematopoiesis ; tumorigenesis ; quiescence ; maturation ; proteins Obor OECD Biochemistry and molecular biology CEP GA20-11931S GA ČR - Grantová agentura ČR LX22NPO5102 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy LM2018129 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy EF18_046/0016045 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora UMG-J - RVO:68378050 UT WOS 001065539400001 EID SCOPUS 85170848706 DOI 10.1038/s41375-023-02030-8 Anotace Hematopoietic stem cells (HSCs) ensure blood cell production during the life-time of an organism, and to do so they need to balance self-renewal, proliferation, differentiation, and migration in a steady state as well as in response to stress or injury. Importantly, aberrant proliferation of HSCs leads to hematological malignancies, and thus, tight regulation by various tumor suppressor pathways, including p53, is essential. Protein phosphatase magnesium-dependent 1 delta (PPM1D) is a negative regulator of p53 and promotes cell survival upon induction of genotoxic stress. Truncating mutations in the last exon of PPM1D lead to the production of a stable, enzymatically active protein and are commonly associated with clonal hematopoiesis. Using a transgenic mouse model, we demonstrate that truncated PPM1D reduces self-renewal of HSCs in basal conditions but promotes the development of aggressive AML after exposure to ionizing radiation. Inhibition of PPM1D suppressed the colony growth of leukemic stem and progenitor cells carrying the truncated PPM1D, and remarkably, it provided protection against irradiation-induced cell growth. Altogether, we demonstrate that truncated PPM1D affects HSC maintenance, disrupts normal hematopoiesis, and that its inhibition could be beneficial in the context of therapy-induced AML. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2024 Elektronická adresa https://www.nature.com/articles/s41375-023-02030-8
Počet záznamů: 1