ArticleCell2026
Inhibition of heme biosynthesis triggers cuproptosis in acute myeloid leukemia.
Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed.
- Lactate metabolism regulation enhances cuproptosis to activate antitumor immunity: Synergistic therapy of hyaluronic acid nanomicelles delivering lactate oxidase/copper-doped carbon dots combined with α-PD-L1 inhibits distant tumors.Materials today. Bio · 2026Article
- AARS2-SIRT5-Driven DLD K445 Lactylation Promotes Cuproptosis Resistance in Glioblastoma Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Iron, Copper, and Zinc Dyshomeostasis in Cardiovascular and Cerebrovascular Diseases: Redox Mechanisms, Evidence Levels, and Translational Prospects.International journal of molecular sciences · 2026Review
- Blastocyst-Derived Lactic Acid Regulates Uterine Epithelial Receptivity and Stromal Decidualization via the HIF1α-HO-1-Heme Metabolic Axis.Antioxidants (Basel, Switzerland) · 2026Article
- A cuproptosis-inducing covalent organic framework synergizes with oncolytic virus for tumor radiotherapy.Nature communications · 2026Article
- PIEZO1 is Required for Acute Myeloid Leukemia Progression and Leukemia Stem Cell Maintenance via HIF1A-SLC7A11 Axis-Mediated Ferroptosis Defense.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Copper dependency in leukemia metabolism.Nature cancer · 2026Article
- Copper homeostasis and cuproptosis rewire the tumor microenvironment: mechanisms, immune modulation, and therapeutic opportunities.Journal of hematology & oncology · 2026Review
- Metal-dependent regulated cell death: Molecular architecture and translational frontiers.iMeta · 2026Review
- Regulated cell death programs shaping cancer therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Acetylated mitochondrial MDH2 regulates CTR2 transcription to induce cuproptosis during Escherichia coli infection.Nature communications · 2026Article
- Localized heme sensing through a ternary molecular glue.bioRxiv : the preprint server for biology · 2026Article
- Dynamic assessment of the allocation of copper to cytochrome c oxidase using size-exclusion chromatography (SEC) combined with inductively coupled plasma mass spectrometry (ICP-MS).The Journal of biological chemistry · 2026Article
- Lysophosphatidylcholine acyltransferase 1 promotes head and neck squamous cell carcinoma progression by enhancing COX17-dependent oxidative phosphorylation.Cell death discovery · 2026Article
- Heme, copper, and a new way to kill cancer cells.EXO : beyond the cell · 2026Article
- Copper homeostasis in macrophages: regulatory mechanisms and immunological implications.Frontiers in chemistry · 2026Review
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Authors and funding
30 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ubiquitous metabolite heme has diverse enzymatic and signaling functions in most mammalian cells. Through integrated analyses of mouse models, human cell lines, and primary patient samples, we identify de novo heme biosynthesis as a selective dependency in acute myeloid leukemia (AML). The dependency is underpinned by a propensity of AML cells, and especially leukemic stem cells (LSCs), to downregulate heme biosynthesis enzymes (HBEs), which promotes their self-renewal. Inhibition of HBEs causes the collapse of mitochondrial Complex IV and dysregulates the copper-chaperone system, inducing cuproptosis, a form of programmed cell death brought about by the oligomerization of lipoylated proteins by copper. Moreover, we identify pathways that are synthetic lethal with heme biosynthesis, including glycolysis, which can be leveraged for combination strategies. Altogether, our work uncovers a heme rheostat that is connected to gene expression and drug sensitivity in AML and implicates HBE inhibition as a trigger of cuproptosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.