ArticleLeukemia2022
Cystine uptake inhibition potentiates front-line therapies in acute myeloid leukemia.
Article in Leukemia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 96 citations in OpenAlex.
- Unraveling the role of glutamine metabolism in cancer: from cell death mechanisms to tumor microenvironment modulation.Experimental hematology & oncology · 2026Review
- A novel role for transcription factor NFE2 in redox regulation and chemotherapy resistance in acute myeloid leukemia.Leukemia · 2026Article
- Experimental Detection Methods and Clinical Translational Challenges of Disulfidptosis in Cancer.Cells · 2026Review
- Genetic mutations governing ferroptosis sensitivity and resistance: a precision approach to cancer therapy.Cell death & disease · 2026Review
- Dual targeting of GPX4 and TXNRD1 triggers eradication of AML cells through induction of apoptosis and ferroptosis.Experimental hematology & oncology · 2026Article
- Targeting ferroptosis in cancer: from mechanistic insights to therapeutic approaches.Molecular biomedicine · 2026Review
- Sonogenic malate depleting modulator for tumor metabolic reprogramming and antitumor immune activation.Bioactive materials · 2026Article
- Harnessing ferroptosis for cancer therapy: Mechanisms and therapeutic strategies (Review).Oncology reports · 2026Review
- Ferroptosis in hematological malignancies: molecular mechanisms and therapeutic potential.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Nucleophosmin 1 lactylation in graft kidney induces ferroptotic trigger waves that exacerbate delayed graft function.Nature communications · 2025Article
- Ferroptosis in cancer: metabolism, mechanisms and therapeutic prospects.Molecular cancer · 2025Review
- Targeting cell death pathways in acute myeloid leukemia: Molecular mechanisms and clinical implications (Review).Oncology reports · 2025Review
- Target practice: Opportunities for therapeutic intervention in CHIP and CCUS.Blood reviews · 2025Review
- Ferroptosis in AML: nanoparticles, biomarkers, and immune rewiring for therapeutic breakthroughs.Discover oncology · 2025Review
- The multiplex crosstalk between non-coding RNAs, programmed cell death and related mechanisms: a dynamic duo in hematological malignancies.Cancer cell international · 2025Review
- A novel prognostic signature integrating disulfidptosis- and ferroptosis-related genes in acute myeloid leukemia.Clinical and experimental medicine · 2025Article
- Ferroptosis: a novel therapeutic warrior in the battle against leukemia.Apoptosis : an international journal on programmed cell death · 2025Review
- NRF2 maintains redox balance via ME1 and NRF2 inhibitor synergizes with venetoclax in NPM1-mutated acute myeloid leukemia.Cancer & metabolism · 2025Article
- Disulfidptosis in pediatric AML: a multi-omics approach to risk stratification and potential therapeutic strategy.Cancer cell international · 2025Article
- N-terminomics and proteomics analysis of Calpain-2 reveal key proteolytic processing of metabolic and cell adhesion proteins.Protein science : a publication of the Protein Society · 2025Article
Corrections and comments
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Authors and funding
37 authors at 6 institutions in 3 countries.
Funding
Abstract
By querying metabolic pathways associated with leukemic stemness and survival in multiple AML datasets, we nominated SLC7A11 encoding the xCT cystine importer as a putative AML dependency. Genetic and chemical inhibition of SLC7A11 impaired the viability and clonogenic capacity of AML cell lines in a cysteine-dependent manner. Sulfasalazine, a broadly available drug with xCT inhibitory activity, had anti-leukemic activity against primary AML samples in ex vivo cultures. Multiple metabolic pathways were impacted upon xCT inhibition, resulting in depletion of glutathione pools in leukemic cells and oxidative stress-dependent cell death, only in part through ferroptosis. Higher expression of cysteine metabolism genes and greater cystine dependency was noted in NPM1-mutated AMLs. Among eight anti-leukemic drugs, the anthracycline daunorubicin was identified as the top synergistic agent in combination with sulfasalazine in vitro. Addition of sulfasalazine at a clinically relevant concentration significantly augmented the anti-leukemic activity of a daunorubicin-cytarabine combination in a panel of 45 primary samples enriched in NPM1-mutated AML. These results were confirmed in vivo in a patient-derived xenograft model. Collectively, our results nominate cystine import as a druggable target in AML and raise the possibility to repurpose sulfasalazine for the treatment of AML, notably in combination with chemotherapy.
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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.