ArticleCancer research2023
Oxidative Phosphorylation Fueled by Fatty Acid Oxidation Sensitizes Leukemic Stem Cells to Cold.
Article in Cancer research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed.
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- Ionomycin suppresses cancer cell growth by disrupting mitochondrial transcription.FEBS open bio · 2026Article
- TIAR-dependent coordination of alternative splicing and lipid peroxidation is required for CML cell resistance to imatinib in the bone marrow stroma.bioRxiv : the preprint server for biology · 2026Article
- Integrated proteogenomic and metabolomic profiling of acute myeloid leukemias to identify molecular subtypes and associated therapy targets.Nature cancer · 2026Article
- Inhibition of ADSS2-mediated de novo AMP biosynthesis re-sensitizes acute myeloid leukemia to BH3 mimetics.Nature cancer · 2026Article
- TIM-3 in AML: a janus-faced orchestrator of immune exhaustion and leukemic self-renewal.Cancer cell international · 2026Review
- Hematopoietic Aging and Leukemia: Mechanistic and Therapeutic Insights.International journal of molecular sciences · 2026Review
- Plasticity, signaling, and metabolic rewiring in melanoma persister cells.Communications biology · 2026Review
- BCAA catabolism mediates POU2AF1 propionylation to enhance T-ALL development.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- ΔNp73 isoform defines a TP53-mutant-like poor-risk subgroup of acute myeloid leukemia.Cell reports. Medicine · 2026Article
- The tumor microenvironment in leukemia: molecular pathways of immune evasion.Frontiers in immunology · 2026Review
- Identification and validation of core oxidative phosphorylation-related genes as biomarkers for immune response and diagnosis in burn injury.Frontiers in immunology · 2026Article
- Metabolomics of healthy hematopoietic stem cells and leukemic stem cells.Journal of clinical and translational research · 2025Article
- Unraveling lipid metabolism for acute myeloid leukemia therapy.Current opinion in hematology · 2025Review
- Tyrosine Kinase Inhibitor Therapy Enhances Stem Cells Profile and May Contribute to Survival of Chronic Myeloid Leukemiastem Cells.Journal of clinical medicine · 2025Article
- Isolation of high-purity muscle stem cells through ice-cold treatment method for the production of cell cultured meat.Current research in food science · 2025Article
- Multiomics analyses reveal adipose-derived stem cells inhibit the inflammatory response of M1-like macrophages through secreting lactate.Stem cell research & therapy · 2024Article
- Metabolic dependencies of acute myeloid leukemia stem cells.International journal of hematology · 2024Review
- Aldehyde Dehydrogenase Genes as Prospective Actionable Targets in Acute Myeloid Leukemia.Genes · 2023Article
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18 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Dependency on mitochondrial oxidative phosphorylation (OxPhos) is a potential weakness for leukemic stem cells (LSC) that can be exploited for therapeutic purposes. Fatty acid oxidation (FAO) is a crucial OxPhos-fueling catabolic pathway for some acute myeloid leukemia (AML) cells, particularly chemotherapy-resistant AML cells. Here, we identified cold sensitivity at 4°C (cold killing challenge; CKC4), commonly used for sample storage, as a novel vulnerability that selectively kills AML LSCs with active FAO-supported OxPhos while sparing normal hematopoietic stem cells. Cell death of OxPhos-positive leukemic cells was induced by membrane permeabilization at 4°C; by sharp contrast, leukemic cells relying on glycolysis were resistant. Forcing glycolytic cells to activate OxPhos metabolism sensitized them to CKC4. Lipidomic and proteomic analyses showed that OxPhos shapes the composition of the plasma membrane and introduces variation of 22 lipid subfamilies between cold-sensitive and cold-resistant cells. Together, these findings indicate that steady-state energy metabolism at body temperature predetermines the sensitivity of AML LSCs to cold temperature, suggesting that cold sensitivity could be a potential OxPhos biomarker. These results could have important implications for designing experiments for AML research to avoid cell storage at 4°C. SIGNIFICANCE: Mitochondrial metabolism fueled by FAO alters the membrane composition and introduces membrane fragility upon cold exposure in OxPhos-driven AML and in LSCs. See related commentary by Jones, p. 2441.
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