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Abstract #3595

Metabolic Role of ATM in Development of Diffuse Large B-cell Lymphoma

Aditya Jhajharia1, Sui Seng Tee1, Maninder Singh1, Sausan Jaber2, Binny Bhandary3, Brian Polster2, Ronald B. Gartenhaus3,4, Kavita Bhalla3, and Dirk Mayer1
1Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, United States, 2Department of Anesthesiology, University of Maryland, Baltimore, MD, United States, 3Department of Medicine, University of Maryland, Baltimore, MD, United States, 4Veterans Administration Medical Center, Baltimore, MD, United States

Ataxia-telangiectasia mutated (ATM) kinase regulates critical metabolic processes of B-cell lymphoid malignancies. Diffuse large B-cell lymphoma (DLBCL) is clinically a very aggressive tumor subtype. This study investigates the role of ATM in metabolism. Oxygen consumption rate measurements showed decreased respiration in DLBCL cells lacking ATM. MRS of hyperpolarized [1-13C]pyruvate in DLBCL line HLY that were either wild-type or had ATM knocked down showed increased conversion of hyperpolarized pyruvate to lactate in HLY cells lacking ATM. These results indicate that deregulation of mitochondrial structure/function due to ATM deficiency results in metabolic changes and may contribute to the development of cancer.

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