prikaz prve stranice dokumenta Cytarabine-induced differentiation of AML cells depends on Chk1 activation and shares the mechanism with inhibitors of DHODH and pyrimidine synthesis
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Cytarabine-induced differentiation of AML cells depends on Chk1 activation and shares the mechanism with inhibitors of DHODH and pyrimidine synthesis
Scientific Reports, 12 (2022), 1; 11344. https://doi.org/10.1038/s41598-022-15520-z
Tomić, Barbara; Smoljo, Tomislav; Lalić, Hrvoje; Dembitz, Vilma; Batinić, Josip; Batinić, Drago; Bedalov, Antonio; Višnjić, Dora

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Tomić, B., Smoljo, T., Lalić, H., Dembitz, V., Batinić, J., Batinić, D. ... Višnjić, D. (2022). Cytarabine-induced differentiation of AML cells depends on Chk1 activation and shares the mechanism with inhibitors of DHODH and pyrimidine synthesis. Scientific Reports, 12. (1). doi: 10.1038/s41598-022-15520-z

Tomić, Barbara, et al. "Cytarabine-induced differentiation of AML cells depends on Chk1 activation and shares the mechanism with inhibitors of DHODH and pyrimidine synthesis." Scientific Reports, vol. 12, br. 1, 2022. https://doi.org/10.1038/s41598-022-15520-z

Tomić, Barbara, Tomislav Smoljo, Hrvoje Lalić, Vilma Dembitz, Josip Batinić, Drago Batinić, Antonio Bedalov i Dora Višnjić. "Cytarabine-induced differentiation of AML cells depends on Chk1 activation and shares the mechanism with inhibitors of DHODH and pyrimidine synthesis." Scientific Reports 12, br. 1 (2022). https://doi.org/10.1038/s41598-022-15520-z

Tomić, B., et al. (2022) 'Cytarabine-induced differentiation of AML cells depends on Chk1 activation and shares the mechanism with inhibitors of DHODH and pyrimidine synthesis', Scientific Reports, 12(1). doi: 10.1038/s41598-022-15520-z

Tomić B, Smoljo T, Lalić H, Dembitz V, Batinić J, Batinić D, i sur.. Cytarabine-induced differentiation of AML cells depends on Chk1 activation and shares the mechanism with inhibitors of DHODH and pyrimidine synthesis. Scientific Reports [Internet]. 05.07.2022. [pristupljeno 11.04.2024.];12(1). doi: 10.1038/s41598-022-15520-z

B. Tomić, et al., "Cytarabine-induced differentiation of AML cells depends on Chk1 activation and shares the mechanism with inhibitors of DHODH and pyrimidine synthesis", Scientific Reports, vol. 12, br. 1, Srpanj 2022. [Online]. Dostupno na: https://urn.nsk.hr/urn:nbn:hr:105:398814. [Citirano: 11.04.2024.]

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Naslov (engleski)Cytarabine-induced differentiation of AML cells depends on Chk1 activation and shares the mechanism with inhibitors of DHODH and pyrimidine synthesis
AutorBarbara Tomić
AutorTomislav Smoljo
AutorHrvoje Lalić
AutorVilma Dembitz
AutorJosip Batinić
AutorDrago Batinić
AutorAntonio Bedalov
AutorDora Višnjić
Autorova ustanovaSveučilište u Zagrebu
Medicinski fakultet
(KATEDRA ZA FIZIOLOGIJU I IMUNOLOGIJU)
Znanstveno / umjetničko
područje, polje i grana		BIOMEDICINA I ZDRAVSTVO
Temeljne medicinske znanosti
Fiziologija čovjeka
Sažetak (engleski)
Abstract Acute myeloid leukemia (AML) is characterized by arrested differentiation making differentiation therapy a promising treatment strategy. Recent success of inhibitors of mutated isocitrate dehydrogenase (IDH) invigorated interest in differentiation therapy of AML so that several new drugs have been proposed, including inhibitors of dihydroorotate dehydrogenase (DHODH), an enzyme in pyrimidine synthesis. Cytarabine, a backbone of standard AML therapy, is known to induce differentiation at low doses, but the mechanism is not completely elucidated. We have previously reported that 5-aminoimidazole-4-carboxamide ribonucleoside (AICAr) and brequinar, a DHODH inhibitor, induced differentiation of myeloid leukemia by activating the ataxia telangiectasia and Rad3-related (ATR)/checkpoint kinase 1 (Chk1) via pyrimidine depletion. In this study, using immunoblotting, flow cytometry analyses, pharmacologic inhibitors and genetic inactivation of Chk1 in myeloid leukemia cell lines, we show that low dose cytarabine induces differentiation by activating Chk1. In addition, cytarabine induces differentiation ex vivo in a subset of primary AML samples that are sensitive to AICAr and DHODH inhibitor. The results of our study suggest that leukemic cell differentiation stimulated by low doses of cytarabine depends on the activation of Chk1 and thus shares the same pathway as pyrimidine synthesis inhibitors.
Ključne riječi (engleski)
Jezikengleski
Vrsta publikacijeZnanstveni rad - Izvorni znanstveni rad
Status objaveObjavljen
Vrsta recenzijeRecenziran
Verzija publikacijeObjavljena verzija rada (izdavačev PDF)
Naslov časopisaScientific Reports
Brojčani podacivol. 12, br. 1, 11344
e-ISSN2045-2322
DOIhttps://doi.org/10.1038/s41598-022-15520-z
URN:NBNurn:nbn:hr:105:398814
Datum objave publikacije2022-07-05
URL dokumentahttps://www.nature.com/articles/s41598-022-15520-z
Vrsta resursaTekst
Prava pristupaOtvoreni pristup
Uvjeti korištenjaIkona licence Imenovanje 4.0 međunarodna (CC BY 4.0)
Datum i vrijeme pohrane2023-04-13 10:09:48