INTERNATIONAL CONGRESS OF
CancerGenetics
The suppressive role of the bone marrow microenvironment on natural killer cells’ anti-leukemic activity in acute myeloid leukemia
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Maryam Nabigol,1,*
1. Department of Hematology and Blood Bank, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Introduction: Acute myeloid leukemia (AML) is the most prevalent type of acute leukemia in adults, characterized by the uncontrolled growth and incommensurate differentiation of myeloid progenitor cells. Despite advancements in therapeutic methods, AML patients often face low survival rates and relapses. According to the studies, in AML, the malignant bone marrow generates a special microenvironment which can exploit various factors to promote leukemia survival and progression. This microenvironment can also attenuate the function of the immune system’s components such as natural killer cells (NK cells) which results in immune evasion of leukemic cells and consequently relapse. In this paper, we aim to review the mechanisms by which the bone marrow microenvironment (BMM) can impede the anti-leukemic activity of NK cells which results in the AML cells’ escape from the therapy and eventually relapse.
- Methods: We conducted an extensive search in PubMed, Scopus and Google Scholar databases with the keywords “acute myeloid leukemia”, “natural killer cell”, and “bone marrow microenvironment” in the last 5 years to identify the articles relevant to the main topic of this paper.
- Results: The immunosuppressive microenvironment generated by AML cells weakens NK cells function which results in immune evasion. In the BMM, nutrients and oxygen deprivation as well as the release of tumor-derived products interfere with the metabolism and antitumor responses of the NK cells. Despite attempts to combat immunosuppressive effects and enhance NK cells' antitumor capacity, several factors in the BMM such as hypoxia, low glucose concentration, tumor-derived metabolites and cytokines contribute to restricting NK cell's function.
- Conclusion: NK-AML recognition is crucially dependent on the BMM. Therefore, overcoming the BMM suppressive factors, along with developing strategies to increase NK cell's function is crucial for achieving the therapeutic responses in AML.
- Keywords: Acute myeloid leukemia, Bone marrow microenvironment, Natural killer cell
