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
Department of Molecular, Cellular, and Biomedical Sciences, University of New Hampshire, Durham, NH 03824 USA.
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta GA 30322 USA.
J Blood Disord Malig. 2024;2(1). Epub 2024 Apr 15.
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 Flt3 mice with Lep 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.
急性髓系白血病（AML）是一种髓系细胞系的血癌。肥胖的特征是体重增加导致脂肪过度积累。肥胖与包括血癌在内的许多癌症的发病率增加有关。本研究在通过将Flt3小鼠与Lep小鼠杂交构建的新型转基因小鼠模型中评估了肥胖在AML进展中的作用。肥胖的AML小鼠的白血病负担增加。此外，研究确定肥胖上调了神经酰胺介导和1-磷酸神经酰胺介导的NADPH氧化酶2（NOX2）。值得注意的是，氧化途径增加被认为与AML的疾病进展有关。综上所述，本研究表明肥胖与AML进展之间存在直接联系，部分原因是增强了神经酰胺介导的NOX2。
