prikaz prve stranice dokumenta The selective prolyl hydroxylase inhibitor IOX5 stabilizes HIF-1α and compromises development and progression of acute myeloid leukemia
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The selective prolyl hydroxylase inhibitor IOX5 stabilizes HIF-1α and compromises development and progression of acute myeloid leukemia
Nature Cancer, 5 (2024), 6; 916-937. https://doi.org/10.1038/s43018-024-00761-w
Lawson, Hannah; Holt-Martyn, James P.; Dembitz, Vilma; Kabayama, Yuka; Wang, Lydia M.; Bellani, Aarushi; Atwal, Samanpreet; Saffoon, Nadia; Durko, Jozef; van de Lagemaat, Louie N.; De Pace, Azzura L.; Tumber, Anthony; Corner, Thomas; Salah, Eidarus; Arndt, Christine; Brewitz, Lennart; Bowen, Matthew; Dubusse, Louis; George, Derek; Allen, Lewis; Guitart, Amelie V.; Fung, Tsz Kan; So, Chi Wai Eric; Schwaller, Juerg; Gallipoli, Paolo; O’Carroll, Donal; Schofield, Christopher J.; Kranc, Kamil R. Više autora...

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Lawson, H., Holt Martyn, J. P., Dembitz, V., Kabayama, Y., Wang, L. M., Bellani, A. ... Kranc, K. R. (2024). The selective prolyl hydroxylase inhibitor IOX5 stabilizes HIF-1α and compromises development and progression of acute myeloid leukemia. Nature Cancer, 5. (6), 916-937. doi: 10.1038/s43018-024-00761-w

Lawson, Hannah, et al. "The selective prolyl hydroxylase inhibitor IOX5 stabilizes HIF-1α and compromises development and progression of acute myeloid leukemia." Nature Cancer, vol. 5, br. 6, 2024, str. 916-937. https://doi.org/10.1038/s43018-024-00761-w

Lawson, Hannah, James P. Holt Martyn, Vilma Dembitz, Yuka Kabayama, Lydia M. Wang, Aarushi Bellani, Samanpreet Atwal, et al. "The selective prolyl hydroxylase inhibitor IOX5 stabilizes HIF-1α and compromises development and progression of acute myeloid leukemia." Nature Cancer 5, br. 6 (2024): 916-937. https://doi.org/10.1038/s43018-024-00761-w

Lawson, H., et al. (2024) 'The selective prolyl hydroxylase inhibitor IOX5 stabilizes HIF-1α and compromises development and progression of acute myeloid leukemia', Nature Cancer, 5(6), str. 916-937. doi: 10.1038/s43018-024-00761-w

Lawson H, Holt Martyn JP, Dembitz V, Kabayama Y, Wang LM, Bellani A, i sur.. The selective prolyl hydroxylase inhibitor IOX5 stabilizes HIF-1α and compromises development and progression of acute myeloid leukemia. Nature Cancer [Internet]. 18.04.2024. [pristupljeno 15.03.2025.];5(6):916-937. doi: 10.1038/s43018-024-00761-w

H. Lawson, et al., "The selective prolyl hydroxylase inhibitor IOX5 stabilizes HIF-1α and compromises development and progression of acute myeloid leukemia", Nature Cancer, vol. 5, br. 6, str. 916-937, Travanj 2024. [Online]. Dostupno na: https://urn.nsk.hr/urn:nbn:hr:105:467440. [Citirano: 15.03.2025.]

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Naslov (engleski)The selective prolyl hydroxylase inhibitor IOX5 stabilizes HIF-1α and compromises development and progression of acute myeloid leukemia
AutorHannah Lawson
AutorJames P. Holt-Martyn
AutorVilma Dembitz
AutorYuka Kabayama
AutorLydia M. Wang
AutorAarushi Bellani
AutorSamanpreet Atwal
AutorNadia Saffoon
AutorJozef Durko
AutorLouie N. van de Lagemaat
AutorAzzura L. De Pace
AutorAnthony Tumber
AutorThomas Corner
AutorEidarus Salah
AutorChristine Arndt
AutorLennart Brewitz
AutorMatthew Bowen
AutorLouis Dubusse
AutorDerek George
AutorLewis Allen
AutorAmelie V. Guitart
AutorTsz Kan Fung
AutorChi Wai Eric So
AutorJuerg Schwaller
AutorPaolo Gallipoli
AutorDonal O’Carroll
AutorChristopher J. Schofield
AutorKamil R. Kranc
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)
Acute myeloid leukemia (AML) is a largely incurable disease, for which new treatments are urgently needed. While leukemogenesis occurs in the hypoxic bone marrow, the therapeutic tractability of the hypoxia-inducible factor (HIF) system remains undefined. Given that inactivation of HIF-1α/HIF-2α promotes AML, a possible clinical strategy is to target the HIF-prolyl hydroxylases (PHDs), which promote HIF-1α/HIF-2α degradation. Here, we reveal that genetic inactivation of Phd1/Phd2 hinders AML initiation and progression, without impacting normal hematopoiesis. We investigated clinically used PHD inhibitors and a new selective PHD inhibitor (IOX5), to stabilize HIF-α in AML cells. PHD inhibition compromises AML in a HIF-1α-dependent manner to disable pro-leukemogenic pathways, re-program metabolism and induce apoptosis, in part via upregulation of BNIP3. Notably, concurrent inhibition of BCL-2 by venetoclax potentiates the anti-leukemic effect of PHD inhibition. Thus, PHD inhibition, with consequent HIF-1α stabilization, is a promising nontoxic strategy for AML, including in combination with venetoclax.
Ključne riječi (engleski)
Jezikengleski
Vrsta publikacijeZnanstveni rad - Izvorni znanstveni rad
Status objaveObjavljen
Vrsta recenzijeRecenziran
Verzija publikacijeObjavljena verzija rada (izdavačev PDF)
Naslov časopisaNature Cancer
Brojčani podacivol. 5, br. 6, str. 916-937
e-ISSN2662-1347
DOIhttps://doi.org/10.1038/s43018-024-00761-w
URN:NBNurn:nbn:hr:105:467440
Datum objave publikacije2024-04-18
URL dokumentahttps://www.nature.com/articles/s43018-024-00761-w
Vrsta resursaTekst
Prava pristupaOtvoreni pristup
Uvjeti korištenjaIkona licence Imenovanje 4.0 međunarodna (CC BY 4.0)
Datum i vrijeme pohrane2025-03-06 08:38:18