Obesity Promotes the Ceramide-Mediated NADPH Oxidase in Acute Myeloid Leukemia.

Journal of blood disorders and malignancies Pub Date : 2024-01-01 Epub Date: 2024-04-15
Weiyuan Wang, Rachel J Sabol, Alexus M Day, Tamara G Hathorn, Maria N Clark, Sara E Connell, Elena A Mantis, Mariam Traore, Jacqueline M Siciliano, Emma J Arsenault, Noelle T Labrecque, Emily C Sullivan, Andrea L Cote, Paul T Toran, Brian M Barth
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Abstract

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.

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肥胖促进急性髓性白血病中神经酰胺介导的 NADPH 氧化酶的形成
急性髓性白血病(AML)是一种髓系血癌。肥胖症的特征是体重增加导致脂肪过度堆积。肥胖与包括血癌在内的多种癌症发病率增加有关。本研究通过将 Flt3ITD 小鼠与 Lepob/ob 小鼠杂交,在新型转基因小鼠模型中评估了肥胖在急性髓细胞性白血病进展中的作用。肥胖急性髓细胞白血病小鼠的白血病负担加重。此外,研究还发现肥胖会上调神经酰胺介导和神经酰胺-1-磷酸介导的 NADPH 氧化酶 2(NOX2)。值得注意的是,氧化途径的增加已被归因于急性髓细胞性白血病的疾病进展。综上所述,本研究表明肥胖与急性髓细胞性白血病的进展之间存在直接联系,部分原因是神经酰胺介导的 NOX2 增加。
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Obesity Promotes the Ceramide-Mediated NADPH Oxidase in Acute Myeloid Leukemia.
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