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The Role of Bone Marrow Microenvironment (Bmm) Cells in Acute Myeloid Leukemia (Aml) Progression: Immune Checkpoints, Metabolic Checkpoints, and Signaling Pathways Publisher Pubmed



Bakhtiyari M1, 2 ; Liaghat M2, 3 ; Aziziyan F2, 4 ; Shapourian H5 ; Yahyazadeh S6 ; Alipour M7 ; Shahveh S8 ; Malekisheikhabadi F9 ; Halimi H6 ; Forghaniesfidvajani R2 ; Zalpoor H2, 10 ; Nabiafjadi M4 ; Pornour M11, 12
Authors
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Authors Affiliations
  1. 1. Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
  2. 2. Network of Immunity in Infection, Malignancy & Autoimmunity (NIIMA), Universal Scientific Education & Research Network (USERN), Tehran, Iran
  3. 3. Department of Medical Laboratory Sciences, Faculty of Medical Sciences, Kazerun Branch, Islamic Azad University, Kazerun, Iran
  4. 4. Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
  5. 5. Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  6. 6. Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  7. 7. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
  8. 8. American Association of Naturopath Physician (AANP), Washington, DC, United States
  9. 9. Department of Hematology and Blood Banking, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
  10. 10. Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  11. 11. Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, MD, United States
  12. 12. Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, United States

Source: Cell Communication and Signaling Published:2023


Abstract

Acute myeloid leukemia (AML) comprises a multifarious and heterogeneous array of illnesses characterized by the anomalous proliferation of myeloid cells in the bone marrow microenvironment (BMM). The BMM plays a pivotal role in promoting AML progression, angiogenesis, and metastasis. The immune checkpoints (ICs) and metabolic processes are the key players in this process. In this review, we delineate the metabolic and immune checkpoint characteristics of the AML BMM, with a focus on the roles of BMM cells e.g. tumor-associated macrophages, natural killer cells, dendritic cells, metabolic profiles and related signaling pathways. We also discuss the signaling pathways stimulated in AML cells by BMM factors that lead to AML progression. We then delve into the roles of immune checkpoints in AML angiogenesis, metastasis, and cell proliferation, including co-stimulatory and inhibitory ICs. Lastly, we discuss the potential therapeutic approaches and future directions for AML treatment, emphasizing the potential of targeting metabolic and immune checkpoints in AML BMM as prognostic and therapeutic targets. In conclusion, the modulation of these processes through the use of directed drugs opens up new promising avenues in combating AML. Thereby, a comprehensive elucidation of the significance of these AML BMM cells' metabolic and immune checkpoints and signaling pathways on leukemic cells can be undertaken in the future investigations. Additionally, these checkpoints and cells should be considered plausible multi-targeted therapies for AML in combination with other conventional treatments in AML. [MediaObject not available: see fulltext.] © 2023, BioMed Central Ltd., part of Springer Nature.
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