Keywords
Chronic myeloid leukemia
Therapeutic resistance
Tyrosine kinase inhibitors
How to Cite
Copyright © | All rights reserved.
The journal holds the exclusive copyright for the publication of this article under the terms of Brazilian law 9610/98.
Partial reproduction
The use of parts of the texts, figures and questionnaire of the article is free, being mandatory the citation of the authors and journal.
Total reproduction
It is expressly prohibited and must be authorized by the journal.
Abstract
Objective: To identify the role of exosomes in Chronic Myeloid Leukemia (CML), highlighting their origin, impact on disease progression, drug resistance, and therapeutic potential. Methods: Integrative review of articles published between 2013 and 2025, in Portuguese, English, and Spanish, with full-text availability. The guiding question was: "How have exosomes influenced the progression of Chronic Myeloid Leukemia and the treatment of this disease?" The search was conducted in PubMed/MEDLINE, Scopus, Web of Science, and SciELO databases, using the descriptors Exosomes, Chronic Myeloid Leukemia OR CML, and Tyrosine Kinase Inhibitor Resistance (TKIs), combined with "AND". Results: Studies indicate that exosomes modulate the tumor microenvironment in CML, promoting cell proliferation, therapeutic resistance, and hematopoietic niche remodeling. Additionally, they interfere with the immune response by modulating T-cell activation and favoring M2 macrophage expansion, contributing to tumor immune evasion. Emerging therapeutic strategies suggest inhibiting exosome biogenesis or manipulating their content as promising approaches to controlling disease progression. Final considerations: Exosomes play a central role in CML progression and therapeutic resistance, making them promising targets for new therapies. Further studies are needed to characterize their molecular content and evaluate therapeutic interventions based on their modulation.
References
ALLEGRA A, et al. Specialized intercellular communications via tunnelling nanotubes in acute and chronic leukemia. Cancers, 2022; 14(3): 659.
BELLAVIA D, et al. Interleukin 3 receptor targeted exosomes inhibit in vitro and in vivo Chronic Myelogenous Leukemia cell growth. Theranostics, 2017; 7(5): 1333–45.
BERNARDI S, et al. Extracellular vesicles in the Chronic Myeloid Leukemia scenario: an update about the shuttling of disease markers and therapeutic molecules. Frontiers in Oncology, 2024; 13: 1239042.
BISSIG C, GRUENBERG J. ALIX and the multivesicular endosome: ALIX in Wonderland. Trends in Cell Biology, 2014; 24(1): 19–25.
CHAI C, et al. BCR-ABL1-driven exosome miR130b 3p mediated gap junction Cx43 MSC intercellular communications imply therapies of leukemic subclonal evolution. Theranostics, 2023; 13(12): 3943–3963.
CHEN X, et al. HucMSC exosomes promoted imatinib induced apoptosis in K562 R cells via a miR 145a 5p/USP6/GLS1 axis. Cell Death & Disease, 2022; 13: 92.
CHENG Y, SCHOREY JS. Exosomes carrying mycobacterial antigens can protect mice against Mycobacterium tuberculosis infection. European Journal of Immunology, 2013; 43(12): 3279–90.
CORRADO C, et al. Chronic myelogenous leukaemia exosomes modulate bone marrow microenvironment through activation of epidermal growth factor receptor. Journal of Cellular and Molecular Medicine, 2016; 20(10): 1829–39.
FAROOQI AA, et al. Exosome biogenesis, bioactivities and functions as new delivery systems of natural compounds. Biotechnology Advances, 2018; 36(1): 328–34.
GAO X, et al. Chronic myelogenous leukemia cells remodel the bone marrow niche via exosome mediated transfer of miR 320. Theranostics, 2019; 9(19): 5642–56.
HRDINOVA T, et al. Exosomes released by imatinib resistant K562 cells contain specific membrane markers, IFITM3, CD146 and CD36 and increase the survival of imatinib sensitive cells in the presence of imatinib. International Journal of Oncology, 2021; 58(2): 238–250.
JABBOUR E, KANTARJIAN H. Chronic myeloid leukemia: 2020 update on diagnosis, therapy and monitoring. American Journal of Hematology, 2020; 95(6): 691–709.
JAFARZADEH N, et al. CML derived exosomes promote tumor favorable functional performance in T cells. BMC Cancer, 2021; 21(1): 1002.
JAFARZADEH N, et al. Alteration of cellular and immune related properties of bone marrow mesenchymal stem cells and macrophages by K562 chronic myeloid leukemia cell derived exosomes. Journal of Cellular Physiology, 2019; 234(4): 3697–710.
JIMENEZ AJ, et al. ESCRT machinery is required for plasma membrane repair. Science, 2014; 343(6174): 1247136.
KARABAY AZ, et al. Identification of exosomal microRNAs and related hub genes associated with imatinib resistance in chronic myeloid leukemia. Naunyn-Schmiedeberg's Archives of Pharmacology, 2024; 397(12): 9701–9721.
KANG KW, et al. The potential of exosomes derived from chronic myelogenous leukemia cells as a biomarker. Anticancer Research, 2018; 38(7): 3935–42.
KALLURI R, LEBLEU VS. The biology, function, and biomedical applications of exosomes. Science, 2020; 367(6478): eaau6977.
KORDELAS L, et al. MSC derived exosomes: a novel tool to treat therapy refractory graft versus host disease. Leukemia, 2014; 28(4): 970–3.
LIU Y, et al. Exosomes from mesenchymal stromal cells enhance imatinib induced apoptosis in human leukemia cells via activation of caspase signaling pathway. Cytotherapy, 2018; 20(2): 181–8.
LYU T, et al. Research progress on exosomes derived from mesenchymal stem cells in hematological malignancies. Hematology/Oncology, 2021; 39(2): 162–9.
MATHIEU M, et al. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell to cell communication. Nature Cell Biology, 2019; 21(1): 9–17.
MIN QH, et al. Exosomes derived from imatinib resistant chronic myeloid leukemia cells mediate a horizontal transfer of drug resistant trait by delivering miR 365. Experimental Cell Research, 2018; 362(2): 386–93.
PATEL GK, et al. Exosomes: Key supporters of tumor metastasis. In: AMIJI M, RAMESH R, editors. Diagnostic and Therapeutic Applications of Exosomes in Cancer. 1st ed. Amsterdam, Netherlands: Elsevier; 2018. p. 261–83.
RAIMONDO S, et al. Chronic myeloid leukemia derived exosomes promote tumor growth through an autocrine mechanism. Cell Communication and Signaling, 2015; 13: 8.
RAFAEL MARTÍNEZ-FONSECA, et al. Bayesian analysis of the effect of exosomes in a mouse xenograft model of chronic myeloid leukemia. Mathematical Biosciences and Engineering, 2023; 20(11): 19504–19526.
ROMA-RODRIGUES C, et al. Exploring RAB11A pathway to hinder chronic myeloid leukemia induced angiogenesis in vivo. Pharmaceutics, 2023; 15(3): 742.
SMYTH LA, et al. CD73 expression on extracellular vesicles derived from CD4⁺ CD25⁺ Foxp3⁺ T cells contributes to their regulatory function. European Journal of Immunology, 2013; 43(9): 2430–40.
SOUSA D, et al. Intercellular transfer of cancer drug resistance traits by extracellular vesicles. Trends in Molecular Medicine, 2015; 21(10): 595–608.
TADOKORO H, et al. Exosomes derived from hypoxic leukemia cells enhance tube formation in endothelial cells. Journal of Biological Chemistry, 2013; 288(48): 34343–51.
TKACH M, et al. Qualitative differences in T cell activation by dendritic cell derived extracellular vesicle subtypes. The EMBO Journal, 2017; 36(20): 3012–28.
UMEZU T, et al. Leukemia cell to endothelial cell communication via exosomal miRNAs. Oncogene, 2013; 32(22): 2747–55.
VAN NIEL G, et al. Shedding light on the cell biology of extracellular vesicles. Nature Reviews Molecular Cell Biology, 2018; 19(4): 213–28.
YU B, et al. Exosomes derived from mesenchymal stem cells. International Journal of Molecular Sciences, 2014; 15(3): 4142–57.
YANG C, et al. Focus on exosomes: novel pathogenic components of leukemia. American Journal of Cancer Research, 2019; 9(8): 1815–29.
YANG K, FU LW. Mechanisms of resistance to BCR-ABL TKIs and the therapeutic strategies: A review. Critical Reviews in Oncology/Hematology, 2015; 93(3): 277–92.
ZHANG F, et al. Exosomes derived from human bone marrow mesenchymal stem cells transfer miR 222 3p to suppress acute myeloid leukemia cell proliferation by targeting IRF2/INPP4B. Molecular and Cellular Probes, 2020; 51: 101513.
ZHANG Y, et al. Exosomes: biogenesis, biologic function and clinical potential. Cell & Bioscience, 2019; 9(1): 19.