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. Gartenhaus^3,4, 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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