Transforming the Niche: The Emerging Role of Extracellular Vesicles in Acute Myeloid Leukaemia Progression

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Apr 27

PMID 38674015

Authors

Manuel Mendes

Ana C Monteiro

Estrela Neto

Cristina C Barrias

Manuel A Sobrinho-Simoes

Delfim Duarte

Hugo R Caires

Affiliations

Soon will be listed here.

Abstract

Acute myeloid leukaemia (AML) management remains a significant challenge in oncology due to its low survival rates and high post-treatment relapse rates, mainly attributed to treatment-resistant leukaemic stem cells (LSCs) residing in bone marrow (BM) niches. This review offers an in-depth analysis of AML progression, highlighting the pivotal role of extracellular vesicles (EVs) in the dynamic remodelling of BM niche intercellular communication. We explore recent advancements elucidating the mechanisms through which EVs facilitate complex crosstalk, effectively promoting AML hallmarks and drug resistance. Adopting a temporal view, we chart the evolving landscape of EV-mediated interactions within the AML niche, underscoring the transformative potential of these insights for therapeutic intervention. Furthermore, the review discusses the emerging understanding of endothelial cell subsets' impact across BM niches in shaping AML disease progression, adding another layer of complexity to the disease progression and treatment resistance. We highlight the potential of cutting-edge methodologies, such as organ-on-chip (OoC) and single-EV analysis technologies, to provide unprecedented insights into AML-niche interactions in a human setting. Leveraging accumulated insights into AML EV signalling to reconfigure BM niches and pioneer novel approaches to decipher the EV signalling networks that fuel AML within the human context could revolutionise the development of niche-targeted therapy for leukaemia eradication.

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References

Peng Y, Wu S, Li Y, Crane J . Type H blood vessels in bone modeling and remodeling. Theranostics. 2020; 10(1):426-436. PMC: 6929606. DOI: 10.7150/thno.34126. View

Zhang Y, Liu Y, Liu H, Tang W . Exosomes: biogenesis, biologic function and clinical potential. Cell Biosci. 2019; 9:19. PMC: 6377728. DOI: 10.1186/s13578-019-0282-2. View

Lenzini S, Debnath K, Joshi J, Wong S, Srivastava K, Geng X . Cell-Matrix Interactions Regulate Functional Extracellular Vesicle Secretion from Mesenchymal Stromal Cells. ACS Nano. 2021; 15(11):17439-17452. PMC: 9023614. DOI: 10.1021/acsnano.1c03231. View

Lu W, Wan Y, Li Z, Zhu B, Yin C, Liu H . Growth differentiation factor 15 contributes to marrow adipocyte remodeling in response to the growth of leukemic cells. J Exp Clin Cancer Res. 2018; 37(1):66. PMC: 5863796. DOI: 10.1186/s13046-018-0738-y. View

Tomasoni C, Arsuffi C, Donsante S, Corsi A, Riminucci M, Biondi A . AML alters bone marrow stromal cell osteogenic commitment via Notch signaling. Front Immunol. 2023; 14:1320497. PMC: 10725948. DOI: 10.3389/fimmu.2023.1320497. View

Madeo M, Colbert P, Vermeer D, Lucido C, Cain J, Vichaya E . Cancer exosomes induce tumor innervation. Nat Commun. 2018; 9(1):4284. PMC: 6191452. DOI: 10.1038/s41467-018-06640-0. View

Dohner H, Wei A, Appelbaum F, Craddock C, DiNardo C, Dombret H . Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022; 140(12):1345-1377. DOI: 10.1182/blood.2022016867. View

Ossenkoppele G, Stussi G, Maertens J, van Montfort K, Biemond B, Breems D . Addition of bevacizumab to chemotherapy in acute myeloid leukemia at older age: a randomized phase 2 trial of the Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON) and the Swiss Group for Clinical Cancer Research (SAKK). Blood. 2012; 120(24):4706-11. DOI: 10.1182/blood-2012-04-420596. View

Wang Y, Gao A, Zhao H, Lu P, Cheng H, Dong F . Leukemia cell infiltration causes defective erythropoiesis partially through MIP-1α/CCL3. Leukemia. 2016; 30(9):1897-908. DOI: 10.1038/leu.2016.81. View

10.

Larey A, Spoerer T, Daga K, Morfin M, Hynds H, Carpenter J . High throughput screening of mesenchymal stromal cell morphological response to inflammatory signals for bioreactor-based manufacturing of extracellular vesicles that modulate microglia. Bioact Mater. 2024; 37:153-171. PMC: 10972802. DOI: 10.1016/j.bioactmat.2024.03.009. View

11.

Burger J, Burkle A . The CXCR4 chemokine receptor in acute and chronic leukaemia: a marrow homing receptor and potential therapeutic target. Br J Haematol. 2007; 137(4):288-96. DOI: 10.1111/j.1365-2141.2007.06590.x. View

12.

Vasconcelos M, Caires H, Abols A, Xavier C, Line A . Extracellular vesicles as a novel source of biomarkers in liquid biopsies for monitoring cancer progression and drug resistance. Drug Resist Updat. 2019; 47:100647. DOI: 10.1016/j.drup.2019.100647. View

13.

Liu Y, Yuan X, Munoz N, Logan T, Ma T . Commitment to Aerobic Glycolysis Sustains Immunosuppression of Human Mesenchymal Stem Cells. Stem Cells Transl Med. 2018; 8(1):93-106. PMC: 6312448. DOI: 10.1002/sctm.18-0070. View

14.

Braga C, da Silva L, Santos R, de Carvalho L, Mandacaru S, de Oliveira Trugilho M . Proteomics profile of mesenchymal stromal cells and extracellular vesicles in normoxic and hypoxic conditions. Cytotherapy. 2022; 24(12):1211-1224. DOI: 10.1016/j.jcyt.2022.08.009. View

15.

Kumar B, Garcia M, Weng L, Jung X, Murakami J, Hu X . Acute myeloid leukemia transforms the bone marrow niche into a leukemia-permissive microenvironment through exosome secretion. Leukemia. 2017; 32(3):575-587. PMC: 5843902. DOI: 10.1038/leu.2017.259. View

16.

Morikawa S, Mabuchi Y, Kubota Y, Nagai Y, Niibe K, Hiratsu E . Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow. J Exp Med. 2009; 206(11):2483-96. PMC: 2768869. DOI: 10.1084/jem.20091046. View

17.

Hiram-Bab S, Liron T, Deshet-Unger N, Mittelman M, Gassmann M, Rauner M . Erythropoietin directly stimulates osteoclast precursors and induces bone loss. FASEB J. 2015; 29(5):1890-900. DOI: 10.1096/fj.14-259085. View

18.

Piotrowska K, Tarnowski M . Bone Marrow Adipocytes-Role in Physiology and Various Nutritional Conditions in Human and Animal Models. Nutrients. 2021; 13(5). PMC: 8146898. DOI: 10.3390/nu13051412. View

19.

Kellaway S, Potluri S, Keane P, Blair H, Ames L, Worker A . Leukemic stem cells activate lineage inappropriate signalling pathways to promote their growth. Nat Commun. 2024; 15(1):1359. PMC: 10867020. DOI: 10.1038/s41467-024-45691-4. View

20.

Mulcahy L, Pink R, Carter D . Routes and mechanisms of extracellular vesicle uptake. J Extracell Vesicles. 2014; 3. PMC: 4122821. DOI: 10.3402/jev.v3.24641. View