ArticleBlood2022
The STAT3-MYC axis promotes survival of leukemia stem cells by regulating SLC1A5 and oxidative phosphorylation.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 124 citations in OpenAlex.
- PPRC1 is a prognostic biomarker and key regulator of mitochondrial oxidative phosphorylation in multiple myeloma.Annals of medicine · 2026Article
- ANKRD28 interacts with DOCK180 to activate Rac1-STAT3-Myc signaling and sustain stemness of CD34Molecular and cellular biochemistry · 2026Article
- Upadacitinib Restrains the Pathogenic Fitness of CD4Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Unraveling the role of glutamine metabolism in cancer: from cell death mechanisms to tumor microenvironment modulation.Experimental hematology & oncology · 2026Review
- Plumbagin Is a PKM2 Activator That Modulates Glutamine Metabolism and Dependency in Leukemia.Metabolites · 2026Article
- PAPOLA-mediated hyperactive polyadenylation promotes leukemogenesis and leukemia stem cell self-renewal through metabolic reprogramming.Nature cancer · 2026Article
- MYC in Oncogenesis and Therapeutic Implications.MedComm · 2026Review
- Cancer-Associated STAT3 Mutations Maintain ES Cell Self-Renewal Through Phosphorylation-Independent Mechanisms.Genes to cells : devoted to molecular & cellular mechanisms · 2026Article
- Transcription factors remodel tumor immune microenvironment by impacting multiple immune cells.Discover oncology · 2026Review
- Complement C5a/C5aR1 pathway facilitates glioblastoma progression via fostering glioma stem cell-macrophage symbiosis.Journal of neuroinflammation · 2026Article
- Targeting STAT3-mediated lipid metabolism reprogramming overcomes chemoresistance in acute myeloid leukemia.Cell death & disease · 2026Article
- HDAC8 inhibition targets STAT3-MYC axis and synergizes with Venetoclax in KMT2A-rearranged acute myeloid leukemia.Leukemia · 2026Article
- TENT5A Maintains MYC mRNA Stability to Enhance Osteosarcoma Stemness.Cancer research · 2026Article
- ERK1/2 hijack STAT3 via Thr714 phosphorylation to suppress gene expression.Cell communication and signaling : CCS · 2026Article
- Targeting the Glutamine Transporter SLC1A5 Enhances Sensitivity of Acute Myeloid Leukemia to MLN4924.Biomedicines · 2026Article
- Beating the STATs: targeting the metabolome in acute myeloid leukemia.Haematologica · 2026Article
- The STAT3-VDAC1 axis modulates mitochondrial function and plays a critical role in the survival of acute myeloid leukemia cells.Haematologica · 2026Article
- Review
- Identifying the therapeutic potential of niclosamide in overcoming IFN-gamma dependent cancer immune evasion in the tumor microenvironment.Frontiers in immunology · 2026Article
- High-Throughput Metabolomics in Transfusion Medicine.Methods in molecular biology (Clifton, N.J.) · 2026Article
39 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
Acute myeloid leukemia (AML) is characterized by the presence of leukemia stem cells (LSCs), and failure to fully eradicate this population contributes to disease persistence/relapse. Prior studies have characterized metabolic vulnerabilities of LSCs, which demonstrate preferential reliance on oxidative phosphorylation (OXPHOS) for energy metabolism and survival. In the present study, using both genetic and pharmacologic strategies in primary human AML specimens, we show that signal transducer and activator of transcription 3 (STAT3) mediates OXPHOS in LSCs. STAT3 regulates AML-specific expression of MYC, which in turn controls transcription of the neutral amino acid transporter gene SLC1A5. We show that genetic inhibition of MYC or SLC1A5 acts to phenocopy the impairment of OXPHOS observed with STAT3 inhibition, thereby establishing this axis as a regulatory mechanism linking STAT3 to energy metabolism. Inhibition of SLC1A5 reduces intracellular levels of glutamine, glutathione, and multiple tricarboxylic acid (TCA) cycle metabolites, leading to reduced TCA cycle activity and inhibition of OXPHOS. Based on these findings, we used a novel small molecule STAT3 inhibitor, which binds STAT3 and disrupts STAT3-DNA, to evaluate the biological role of STAT3. We show that STAT3 inhibition selectively leads to cell death in AML stem and progenitor cells derived from newly diagnosed patients and patients who have experienced relapse while sparing normal hematopoietic cells. Together, these findings establish a STAT3-mediated mechanism that controls energy metabolism and survival in primitive AML cells.
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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.