Old drug, new parasite: targeting leukemia with antifungals
(2026) Blood — Vol. 147, n° 21, p. 2417-2418 (2026)
Files
van Gastel_Blood Commentary Himonas et al_postprint.pdf
Open Access - Adobe PDF
- 50.24 KB
Details
- Authors
- Abstract
- In this issue of Blood, Himonas et al identify antifungal agents as potent inhibitors of mitochondrial metabolism in acute myeloid leukemia (AML) cells, offering new therapeutic options through drug repurposing. 1 Leukemic transformation of hematopoietic cells is accompanied by extensive metabolic reprogramming, which commonly features changes in mitochondrial oxidative phosphorylation (OXPHOS) activity. 2 OXPHOS encompasses two closely-coupled biochemical processes: the electron transport chain, where electrons from NADH and FADH₂ are transferred to oxygen through a series of four multi-subunit protein complexes (I-IV) generating a proton gradient across the inner mitochondrial membrane, and chemiosmosis, in which ATP synthase (also known as complex V) uses the energy of the proton gradient to synthesize ATP from ADP and phosphate. In general, AML cells show higher OXPHOS activity compared to their non-malignant counterparts, and this is even more pronounced in leukemic stem cells and in residual AML cells persisting after therapy, creating a particular metabolic vulnerability. 3 Interestingly, complex V in AML mitochondria hydrolyzes ATP rather than generating it. 4 This indicates that maintaining a high mitochondrial membrane potential may be the primary function of OXPHOS in these cells, likely to suppress pro-apoptotic signaling. The high dependency on OXPHOS in AML cells has inspired many therapeutic attempts to exploit this vulnerability. Unfortunately, despite promising preclinical efficacy, recent clinical
- Affiliations
Citations
van Gastel, N. (2026). Old drug, new parasite: targeting leukemia with antifungals. Blood, 147(21), 2417-2418. https://doi.org/10.1182/blood.2026033393 (Original work published 2026)