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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Scientific paper - Original scientific paper
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

Institutional repository: Dr Med - University of Zagreb School of Medicine Digital Repository

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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, no. 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 and 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, no. 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, and 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]. 2022 July 05 [cited 2024 November 25];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, no. 1, July 2022. [Online]. Available at: https://urn.nsk.hr/urn:nbn:hr:105:398814. [Accessed: 25 November 2024]

Metadata
Title (english)Cytarabine-induced differentiation of AML cells depends on Chk1 activation and shares the mechanism with inhibitors of DHODH and pyrimidine synthesis
AuthorBarbara Tomić
AuthorTomislav Smoljo
AuthorHrvoje Lalić
AuthorVilma Dembitz
AuthorJosip Batinić
AuthorDrago Batinić
AuthorAntonio Bedalov
AuthorDora Višnjić
Author's institutionUniversity of Zagreb
School of Medicine
(Department of Physiology and Immunology)
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Human Physiology
Abstract (english)
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.
Keywords (english)
Languageenglish
Publication typeScientific paper - Original scientific paper
Publication statusPublished
Peer reviewPeer review
Publication versionPublished version
Journal titleScientific Reports
Numberingvol. 12, no. 1, 11344
e-ISSN2045-2322
DOIhttps://doi.org/10.1038/s41598-022-15520-z
URN:NBNurn:nbn:hr:105:398814
Publication2022-07-05
Document URLhttps://www.nature.com/articles/s41598-022-15520-z
Type of resourceText
Access conditionsOpen access
Terms of useLicence Attribution 4.0 International (CC BY 4.0) icon
Created on2023-04-13 10:09:48