Glycolysis and immunosenescence: key players in the pathogenesis of acute myeloid leukemia and their therapeutic potential
), Jun Fan1,2()Abstract
Acute myeloid leukemia (AML) is a hematopoietic progenitor cell-affected hematological malignancy, caused by the accumulation of genetic and epigenetic abnormalities leading to impaired cell differentiation, enhanced self-renewal capacity, and uncontrolled proliferation. Despite progress in understanding its biology and therapeutic strategies, the mortality rate remains high, with a five-year survival rate below 30%, and the clonal evolution of cells is complex, exhibiting genetic heterogeneity. Glycolysis plays a central role in the metabolic network of cancer cells. Cancer cells produce energy and substances through glycolysis, and their metabolic product, lactic acid, affects the tumor microenvironment (TME), leading to immune suppression, among other effects. Inhibition of glycolysis can enhance the sensitivity of AML to chemotherapeutic drugs. Aging is a risk factor for many diseases and leads to increased incidence and mortality rates of AML. Elderly patients exhibit greater heterogeneity. In AML, the dysfunction of T cells and NK cells is closely related to treatment responses. The process of T cell senescence is complex, involving various phenomena and mechanisms. Senescent T cells have weakened functions, affecting immune surveillance and TME, leading to reduced responses to chemotherapy. This review summarizes the significance of key glycolytic enzymes and aging in AML-related research.
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