Importance of Glutamine Metabolism in Leukemia Cells by Energy Production Through TCA Cycle and by Redox Homeostasis

Mineaki GotoDepartment of Internal Medicine, Division of Hematology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan

Hiroshi MiwaDepartment of Internal Medicine, Division of Hematology, Aichi Medical University School of Medicine, Nagakute, Aichi, JapanCorrespondence[email protected]

Masato ShikamiDepartment of Internal Medicine, Division of Hematology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan

Norikazu Tsunekawa-ImaiDepartment of Internal Medicine, Division of Hematology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan

Kazuto SuganumaDepartment of Internal Medicine, Division of Hematology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan

Shohei MizunoDepartment of Internal Medicine, Division of Hematology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan

Miyuki TakahashiDepartment of Internal Medicine, Division of Hematology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan

Motonori MizutaniDepartment of Internal Medicine, Division of Hematology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan

Ichiro HanamuraDepartment of Internal Medicine, Division of Hematology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan

Masakazu NittaDepartment of Internal Medicine, Division of Hematology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan

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Abstract

Some cancer cells depend on glutamine despite of pronounced glycolysis. We examined the glutamine metabolism in leukemia cells, and found that HL-60 cells most depended on glutamine in the 4 acute myelogenous leukemia (AML) cell lines examined: growth of HL-60 cells was most suppressed by glutamine deprivation and by inhibition of glutaminolysis, which was rescued by tricarboxylic acid (TCA) cycle intermediate, oxaloacetic acid. Glutamine is also involved in antioxidant defense function by increasing glutathione. Glutamine deprivation suppressed the glutathione content and elevated reactive oxygen species most evidently in HL-60 cells. Glutamine metabolism might be a therapeutic target in some leukemia.

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Importance of Glutamine Metabolism in Leukemia Cells by Energy Production Through TCA Cycle and by Redox Homeostasis

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Importance of Glutamine Metabolism in Leukemia Cells by Energy Production Through TCA Cycle and by Redox Homeostasis

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