ArticleJournal of cellular and molecular medicine2016
Chronic myelogenous leukaemia exosomes modulate bone marrow microenvironment through activation of epidermal growth factor receptor.
Article in Journal of cellular and molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 103 citations in OpenAlex.
- Oxidative Phosphorylation and Fatty Acid Oxidation Are Central to Mitochondrial Metabolism Rewiring in CML Stem/Progenitor Cell Survival.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Review
- Roles of extracellular vesicles in the pathogenesis of chronic myeloid leukemia.Journal of physiology and biochemistry · 2026Review
- The tumor microenvironment in hematologic malignancies: immune evasion, metabolic reprogramming, and therapeutic resistance.Blood science (Baltimore, Md.) · 2026Review
- Exosomes in Osteoarthritis: Emerging Roles in Pathogenesis, Diagnosis, and Therapeutic Potential.Current pharmaceutical design · 2026Review
- Treatment-Free Remission in Chronic Myeloid Leukemia: Revisiting the "W" Questions.European journal of haematology · 2025Review
- Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.Journal of hematology & oncology · 2025Review
- Harnessing the power of exosomes for diagnosis, prognosis, and treatment of hematological malignancies.Stem cell research & therapy · 2025Review
- The role of the hematopoietic stem/progenitor cells-derived extracellular vesicles in hematopoiesis.Heliyon · 2024Article
- Hitting the target: cell signaling pathways modulation by extracellular vesicles.Extracellular vesicles and circulating nucleic acids · 2024Review
- IL-18 and VEGF-A trigger type 2 innate lymphoid cell accumulation and pro-tumoral function in chronic myeloid leukemia.Haematologica · 2023Article
- Renal cancer secretome induces migration of mesenchymal stromal cells.Stem cell research & therapy · 2023Article
- The Bone Marrow Immune Microenvironment in CML: Treatment Responses, Treatment-Free Remission, and Therapeutic Vulnerabilities.Current hematologic malignancy reports · 2023Review
- Tumour‑derived exosomes and their emerging roles in leukaemia (Review).Experimental and therapeutic medicine · 2023Review
- ExploringPharmaceutics · 2023Article
- Application of cell-derived exosomes in the hematological malignancies therapy.Frontiers in pharmacology · 2023Review
- Extracellular vesicles in hematological malignancies: EV-dence for reshaping the tumoral microenvironment.Frontiers in immunology · 2023Review
- Article
- Emerging roles of extracellular vesicles in normal and malignant hematopoiesis.The Journal of clinical investigation · 2022Review
- Extracellular Vesicles in Myeloid Neoplasms.International journal of molecular sciences · 2022Review
- Acute lymphoblastic leukemia-derived extracellular vesicles affect quiescence of hematopoietic stem and progenitor cells.Cell death & disease · 2022Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic myelogenous leukaemia (CML) is a clonal myeloproliferative disorder. Recent evidence indicates that altered crosstalk between CML and mesenchymal stromal cells may affect leukaemia survival; moreover, vesicles released by both tumour and non-tumour cells into the microenvironment provide a suitable niche for cancer cell growth and survival. We previously demonstrated that leukaemic and stromal cells establish an exosome-mediated bidirectional crosstalk leading to the production of IL8 in stromal cells, thus sustaining the survival of CML cells. Human cell lines used are LAMA84 (CML cells), HS5 (stromal cells) and bone marrow primary stromal cells; gene expression and protein analysis were performed by real-time PCR and Western blot. IL8 and MMP9 secretions were evaluated by ELISA. Exosomes were isolated from CML cells and blood samples of CML patients. Here, we show that LAMA84 and CML patients' exosomes contain amphiregulin (AREG), thus activating epidermal growth factor receptor (EGFR) signalling in stromal cells. EGFR signalling increases the expression of SNAIL and its targets, MMP9 and IL8. We also demonstrated that pre-treatment of HS5 with LAMA84 exosomes increases the expression of annexin A2 that promotes the adhesion of leukaemic cells to the stromal monolayer, finally supporting the growth and invasiveness of leukaemic cells. Leukaemic and stromal cells establish a bidirectional crosstalk: exosomes promote proliferation and survival of leukaemic cells, both in vitro and in vivo, by inducing IL8 secretion from stromal cells. We propose that this mechanism is activated by a ligand-receptor interaction between AREG, found in CML exosomes, and EGFR in bone marrow stromal cells.
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