Journal of blood disorders and malignancies · 2024
Obesity Promotes the Ceramide-Mediated NADPH Oxidase in Acute Myeloid Leukemia.
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Wang Weiyuan, Sabol Rachel J, Day Alexus M, Hathorn Tamara G, Clark Maria N, Connell Sara E, Mantis Elena A, Traore Mariam, Siciliano Jacqueline M, Arsenault Emma J, Labrecque Noelle T, Sullivan Emily C, Cote Andrea L, Toran Paul T, Barth Brian M
Аннотация
Acute myeloid leukemia (AML) is a type of blood cancer of the myeloid cell lineage. Obesity is characterized by an increase in body weight that results in excessive fat accumulation. Obesity has been associated with an increased incidence of many cancers, including blood cancers. This study evaluated the role obesity in AML progression in a novel transgenic mouse model developed by crossing Flt3ITD mice with Lepob/ob mice. Leukemia burden was augmented in obese AML mice. In addition, it was determined that obesity upregulated the ceramide-mediated and ceramide-1-phosphate-mediated NADPH oxidase 2 (NOX2). Notably, increased oxidative pathways has been attributed to disease progression in AML. Taken together, this study demonstrates a direct link between obesity and the progression of AML in part by augmenting the ceramide mediated NOX2.