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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Scientific paper - Original scientific paper
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. More authors...

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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, no. 6, 2024, pp. 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, no. 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), pp. 916-937. doi: 10.1038/s43018-024-00761-w

Lawson H, Holt Martyn JP, Dembitz V, Kabayama Y, Wang LM, Bellani A, and sur.. The selective prolyl hydroxylase inhibitor IOX5 stabilizes HIF-1α and compromises development and progression of acute myeloid leukemia. Nature Cancer [Internet]. 2024 April 18 [cited 2025 March 14];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, no. 6, pp. 916-937, April 2024. [Online]. Available at: https://urn.nsk.hr/urn:nbn:hr:105:467440. [Accessed: 14 March 2025]

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Metadata
Title (english)The selective prolyl hydroxylase inhibitor IOX5 stabilizes HIF-1α and compromises development and progression of acute myeloid leukemia
AuthorHannah Lawson
AuthorJames P. Holt-Martyn
AuthorVilma Dembitz
AuthorYuka Kabayama
AuthorLydia M. Wang
AuthorAarushi Bellani
AuthorSamanpreet Atwal
AuthorNadia Saffoon
AuthorJozef Durko
AuthorLouie N. van de Lagemaat
AuthorAzzura L. De Pace
AuthorAnthony Tumber
AuthorThomas Corner
AuthorEidarus Salah
AuthorChristine Arndt
AuthorLennart Brewitz
AuthorMatthew Bowen
AuthorLouis Dubusse
AuthorDerek George
AuthorLewis Allen
AuthorAmelie V. Guitart
AuthorTsz Kan Fung
AuthorChi Wai Eric So
AuthorJuerg Schwaller
AuthorPaolo Gallipoli
AuthorDonal O’Carroll
AuthorChristopher J. Schofield
AuthorKamil R. Kranc
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)
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.
Keywords (english)
Languageenglish
Publication typeScientific paper - Original scientific paper
Publication statusPublished
Peer reviewPeer review
Publication versionPublished version
Journal titleNature Cancer
Numberingvol. 5, no. 6, pp. 916-937
e-ISSN2662-1347
DOIhttps://doi.org/10.1038/s43018-024-00761-w
URN:NBNurn:nbn:hr:105:467440
Publication2024-04-18
Document URLhttps://www.nature.com/articles/s43018-024-00761-w
Type of resourceText
Access conditionsOpen access
Terms of useLicence Attribution 4.0 International (CC BY 4.0) icon
Created on2025-03-06 08:38:18