prikaz prve stranice dokumenta Stearoyl-CoA desaturase inhibition is toxic to acute myeloid leukemia displaying high levels of the de novo fatty acid biosynthesis and desaturation
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Stearoyl-CoA desaturase inhibition is toxic to acute myeloid leukemia displaying high levels of the de novo fatty acid biosynthesis and desaturation
Leukemia, 38 (2024), 11; 2395-2409. https://doi.org/10.1038/s41375-024-02390-9
Dembitz, Vilma; Lawson, Hannah; Burt, Richard; Natani, Sirisha; Philippe, Céline; James, Sophie C.; Atkinson, Samantha; Durko, Jozef; Wang, Lydia M.; Campos, Joana; Magee, Aoife M. S.; Woodley, Keith; Austin, Michael J.; Rio-Machin, Ana; Casado, Pedro; Bewicke-Copley, Findlay; Rodriguez Blanco, Giovanny; Pereira-Martins, Diego; Oudejans, Lieve; Boet, Emeline; von Kriegsheim, Alex; Schwaller, Juerg; Finch, Andrew J.; Patel, Bela; Sarry, Jean-Emmanuel; Tamburini, Jerome; Schuringa, Jan Jacob; Hazlehurst, Lori; Copland III, John A.; Yuneva, Mariia; Peck, Barrie; Cutillas, Pedro; Fitzgibbon, Jude; Rouault-Pierre, Kevin; Kranc, Kamil; Gallipoli, Paolo Više autora...

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Dembitz, V., Lawson, H., Burt, R., Natani, S., Philippe, C., James, S. C. ... Gallipoli, P. (2024). Stearoyl-CoA desaturase inhibition is toxic to acute myeloid leukemia displaying high levels of the de novo fatty acid biosynthesis and desaturation. Leukemia, 38. (11), 2395-2409. doi: 10.1038/s41375-024-02390-9

Dembitz, Vilma, et al. "Stearoyl-CoA desaturase inhibition is toxic to acute myeloid leukemia displaying high levels of the de novo fatty acid biosynthesis and desaturation." Leukemia, vol. 38, br. 11, 2024, str. 2395-2409. https://doi.org/10.1038/s41375-024-02390-9

Dembitz, Vilma, Hannah Lawson, Richard Burt, Sirisha Natani, Céline Philippe, Sophie C. James, Samantha Atkinson, et al. "Stearoyl-CoA desaturase inhibition is toxic to acute myeloid leukemia displaying high levels of the de novo fatty acid biosynthesis and desaturation." Leukemia 38, br. 11 (2024): 2395-2409. https://doi.org/10.1038/s41375-024-02390-9

Dembitz, V., et al. (2024) 'Stearoyl-CoA desaturase inhibition is toxic to acute myeloid leukemia displaying high levels of the de novo fatty acid biosynthesis and desaturation', Leukemia, 38(11), str. 2395-2409. doi: 10.1038/s41375-024-02390-9

Dembitz V, Lawson H, Burt R, Natani S, Philippe C, James SC, i sur.. Stearoyl-CoA desaturase inhibition is toxic to acute myeloid leukemia displaying high levels of the de novo fatty acid biosynthesis and desaturation. Leukemia [Internet]. 26.08.2024. [pristupljeno 04.04.2025.];38(11):2395-2409. doi: 10.1038/s41375-024-02390-9

V. Dembitz, et al., "Stearoyl-CoA desaturase inhibition is toxic to acute myeloid leukemia displaying high levels of the de novo fatty acid biosynthesis and desaturation", Leukemia, vol. 38, br. 11, str. 2395-2409, Kolovoz 2024. [Online]. Dostupno na: https://urn.nsk.hr/urn:nbn:hr:105:358780. [Citirano: 04.04.2025.]

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Naslov (engleski)Stearoyl-CoA desaturase inhibition is toxic to acute myeloid leukemia displaying high levels of the de novo fatty acid biosynthesis and desaturation
AutorVilma Dembitz
AutorHannah Lawson
AutorRichard Burt
AutorSirisha Natani
AutorCéline Philippe
AutorSophie C. James
AutorSamantha Atkinson
AutorJozef Durko
AutorLydia M. Wang
AutorJoana Campos
AutorAoife M. S. Magee
AutorKeith Woodley
AutorMichael J. Austin
AutorAna Rio-Machin
AutorPedro Casado
AutorFindlay Bewicke-Copley
AutorGiovanny Rodriguez Blanco
AutorDiego Pereira-Martins
AutorLieve Oudejans
AutorEmeline Boet
AutorAlex von Kriegsheim
AutorJuerg Schwaller
AutorAndrew J. Finch
AutorBela Patel
AutorJean-Emmanuel Sarry
AutorJerome Tamburini
AutorJan Jacob Schuringa
AutorLori Hazlehurst
AutorJohn A. Copland III
AutorMariia Yuneva
AutorBarrie Peck
AutorPedro Cutillas
AutorJude Fitzgibbon
AutorKevin Rouault-Pierre
AutorKamil Kranc
AutorPaolo Gallipoli
Autorova ustanovaSveučilište u Zagrebu
Medicinski fakultet
(HRVATSKI INSTITUT ZA ISTRAŽIVANJE MOZGA)
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)
Identification of specific and therapeutically actionable vulnerabilities, ideally present across multiple mutational backgrounds, is needed to improve acute myeloid leukemia (AML) patients' outcomes. We identify stearoyl-CoA desaturase (SCD), the key enzyme in fatty acid (FA) desaturation, as prognostic of patients' outcomes and, using the clinical-grade inhibitor SSI-4, show that SCD inhibition (SCDi) is a therapeutic vulnerability across multiple AML models in vitro and in vivo. Multiomic analysis demonstrates that SCDi causes lipotoxicity, which induces AML cell death via pleiotropic effects. Sensitivity to SCDi correlates with AML dependency on FA desaturation regardless of mutational profile and is modulated by FA biosynthesis activity. Finally, we show that lipotoxicity increases chemotherapy-induced DNA damage and standard chemotherapy further sensitizes AML cells to SCDi. Our work supports developing FA desaturase inhibitors in AML while stressing the importance of identifying predictive biomarkers of response and biologically validated combination therapies to realize their full therapeutic potential.
Ključne riječi (engleski)
Jezikengleski
Vrsta publikacijeZnanstveni rad - Izvorni znanstveni rad
Status objaveObjavljen
Vrsta recenzijeRecenziran
Verzija publikacijeObjavljena verzija rada (izdavačev PDF)
Naslov časopisaLeukemia
Brojčani podacivol. 38, br. 11, str. 2395-2409
p-ISSN0887-6924
e-ISSN1476-5551
DOIhttps://doi.org/10.1038/s41375-024-02390-9
URN:NBNurn:nbn:hr:105:358780
Datum objave publikacije2024-08-26
URL dokumentahttps://www.nature.com/articles/s41375-024-02390-9
Vrsta resursaTekst
Prava pristupaOtvoreni pristup
Uvjeti korištenjaIkona licence Imenovanje 4.0 međunarodna (CC BY 4.0)
Datum i vrijeme pohrane2025-03-28 08:06:55