Trial reportThe Journal of biological chemistry2013
Targeting aberrant glutathione metabolism to eradicate human acute myelogenous leukemia cells.
Trial report in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
121 citing papers in PubMed, 198 citations in OpenAlex.
- Article
- A novel role for transcription factor NFE2 in redox regulation and chemotherapy resistance in acute myeloid leukemia.Leukemia · 2026Article
- Elevated mitochondrial protein import in acute myeloid leukemia increases reliance on mitochondrial protease LONP1.The Journal of clinical investigation · 2026Article
- Selective TRPV2 Antagonists Derived from the Natural Product Piperlongumine Inhibit Cancer Cell Migration and Metastasis.ACS chemical biology · 2026Article
- Glutaredoxin 2 is essential for AML survival through mitochondrial permeability transition pore regulation.Blood · 2026Article
- Longitudinal single-cell analysis reveals treatment-resistant stem and mast cells with potential treatments for pediatric AML.Leukemia · 2025Article
- Parthenolide: pioneering new frontiers in hematological malignancies.Frontiers in pharmacology · 2025Review
- Parallel single-cell metabolic analysis and extracellular vesicle profiling reveal vulnerabilities with prognostic significance in acute myeloid leukemia.Nature communications · 2024Article
- Review
- IL-21/IL-21R signaling renders acute myeloid leukemia stem cells more susceptible to cytarabine treatment and CAR T cell therapy.Cell reports. Medicine · 2024Article
- Plant sesquiterpene lactones.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- BMP receptor 2 inhibition regulates mitochondrial bioenergetics to induce synergistic cell death with BCL-2 inhibitors in leukemia and NSLC cells.Research square · 2024Article
- XPO1 inhibition displays anti-leukemia efficacy against DNMT3A-mutant acute myeloid leukemia via downregulating glutathione pathway.Annals of hematology · 2024Article
- The nuclear export protein exportin-1 in solid malignant tumours: From biology to clinical trials.Clinical and translational medicine · 2024Review
- Metabolic Fingerprint in Childhood Acute Lymphoblastic Leukemia.Diagnostics (Basel, Switzerland) · 2024Article
- Piplartine eliminates CD34 + AML stem/progenitor cells by inducing oxidative stress and suppressing NF-κB signalling.Cell death discovery · 2024Article
- Enhancing Leukemia Treatment: The Role of Combined Therapies Based on Amino Acid Starvation.Cancers · 2024Review
- Parthenolide As a Therapeutic for Disseminated Canine Neoplasms.The Journal of pharmacology and experimental therapeutics · 2024Article
- miR-30e-5p regulates leukemia stem cell self-renewal through the Cyb561/ROS signaling pathway.Haematologica · 2024Article
- Mitochondrial abnormalities as a target of intervention in acute myeloid leukemia.Frontiers in oncology · 2024Review
61 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 6 institutions in 1 country.
Funding
Abstract
The development of strategies to eradicate primary human acute myelogenous leukemia (AML) cells is a major challenge to the leukemia research field. In particular, primitive leukemia cells, often termed leukemia stem cells, are typically refractory to many forms of therapy. To investigate improved strategies for targeting of human AML cells we compared the molecular mechanisms regulating oxidative state in primitive (CD34(+)) leukemic versus normal specimens. Our data indicate that CD34(+) AML cells have elevated expression of multiple glutathione pathway regulatory proteins, presumably as a mechanism to compensate for increased oxidative stress in leukemic cells. Consistent with this observation, CD34(+) AML cells have lower levels of reduced glutathione and increased levels of oxidized glutathione compared with normal CD34(+) cells. These findings led us to hypothesize that AML cells will be hypersensitive to inhibition of glutathione metabolism. To test this premise, we identified compounds such as parthenolide (PTL) or piperlongumine that induce almost complete glutathione depletion and severe cell death in CD34(+) AML cells. Importantly, these compounds only induce limited and transient glutathione depletion as well as significantly less toxicity in normal CD34(+) cells. We further determined that PTL perturbs glutathione homeostasis by a multifactorial mechanism, which includes inhibiting key glutathione metabolic enzymes (GCLC and GPX1), as well as direct depletion of glutathione. These findings demonstrate that primitive leukemia cells are uniquely sensitive to agents that target aberrant glutathione metabolism, an intrinsic property of primary human AML cells.
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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.