ArticleAnnals of translational medicine2020
Stromal cells promote chemoresistance of acute myeloid leukemia cells via activation of the IL-6/STAT3/OXPHOS axis.
Article in Annals of translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- Rethinking Drug Resistance in Acute Promyelocytic Leukemia: The Regulated Cell Death Network as an Integrative Framework.Biomolecules · 2026Review
- Exploring the Bone Marrow Microenvironment as a Therapeutic Barrier and Targetable Source of Crosstalk in Acute Myeloid Leukemia.Blood and lymphatic cancer : targets and therapy · 2026Review
- Recent advances in drug delivery and treatment strategies for acute myeloid leukemia.International journal of pharmaceutics · 2025Review
- Targeting bone marrow mesenchymal stromal cell-derived IL-6 to overcome acute myeloid leukemia chemoresistance.Blood advances · 2025Observational
- Synergistic MDM2-STAT3 Inhibition Demonstrates Strong Anti-Leukemic Efficacy in Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2025Article
- Review
- Acute myeloid leukemia mitochondria hydrolyze ATP to support oxidative metabolism and resist chemotherapy.Science advances · 2025Article
- Paediatric bone marrow mesenchymal stem cells support acute myeloid leukaemia cell survival and enhance chemoresistance via contact-independent mechanism.British journal of haematology · 2025Article
- OXPHOS mediators in acute myeloid leukemia patients: Prognostic biomarkers and therapeutic targets for personalized medicine.World journal of surgical oncology · 2024Article
- Anti-CLL1 liposome loaded with miR-497-5p and venetoclax as a novel therapeutic strategy in acute myeloid leukemia.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Metabolic dependencies of acute myeloid leukemia stem cells.International journal of hematology · 2024Review
- The AC010247.2/miR-125b-5p axis triggers the malignant progression of acute myelocytic leukemia by IL-6R.Heliyon · 2024Article
- The role of IL-22 in cancer.Medical oncology (Northwood, London, England) · 2024Review
- Bone marrow inflammation in haematological malignancies.Nature reviews. Immunology · 2024Review
- Single-cell signatures identify microenvironment factors in tumors associated with patient outcomes.Cell reports methods · 2024Article
- Transforming the Niche: The Emerging Role of Extracellular Vesicles in Acute Myeloid Leukaemia Progression.International journal of molecular sciences · 2024Review
- Article
- Targeting metabolic vulnerabilities to overcome resistance to therapy in acute myeloid leukemia.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Novel insights into IL-37: an anti-inflammatory cytokine with emerging roles in anti-cancer process.Frontiers in immunology · 2023Review
- Bone Marrow Microenvironment as a Source of New Drug Targets for the Treatment of Acute Myeloid Leukaemia.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBone marrow stromal cells (BMSCs) are known to promote chemoresistance in acute myeloid leukemia (AML) cells. However, the molecular basis for BMSC-associated AML chemoresistance remains largely unexplored.
methodsThe mitochondrial oxidative phosphorylation (OXPHOS) levels of AML cells were measured by a Seahorse XFe24 cell metabolic analyzer. The activity of total or mitochondrial signal transducer and transcription activator 3 (STAT3) in AML cells was explored by flow cytometry and Western blotting. Real-time quantitative PCR, Western blotting and enzyme-linked immunosorbent assay (ELISA) were used to analyze expression of interleukin 6 (IL-6) in the human BMSC line HS-5, and IL-6 was knocked out in HS-5 cells by CRISPR/Cas9 system.
resultsIn this study, we observed that co-culturing with BMSCs heightened OXPHOS levels in AML cells, thus promoting chemoresistance in these cells. HS-5 cell-induced upregulation of OXPHOS is dependent on the activation of STAT3, especially on that of mitochondrial serine phosphorylated STAT3 (pS-STAT3) in AML cells. The relationship among pS-STAT3, OXPHOS, and chemosensitivity of AML cells induced by BMSCs was demonstrated by the STAT3 activator and inhibitor, which upregulated and downregulated the levels of mitochondrial pS-STAT3 and OXPHOS, respectively. Intriguingly, AML cells remodeled HS-5 cells to secrete more IL-6, which augmented mitochondrial OXPHOS in AML cells and stimulated their chemoresistance. IL-6 knockout in HS-5 cells impaired the ability of these cells to activate STAT3, to increase OXPHOS, or to promote chemoresistance in AML cells.
conclusionsBMSCs promoted chemoresistance in AML cells via the activation of the IL-6/STAT3/OXPHOS pathway. These findings exhibit a novel mechanism of chemoresistance in AML cells in the bone marrow microenvironment from a metabolic perspective.
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