Metabolic inhibition therapy targeting glutaminolysis in mantle cell lymphoma

Motivation: Mantle cell lymphoma (MCL) poses clinical challenges due to resistance to current treatment modalities. Targeting cell metabolism may prove new therapeutic approach to MCL. Goal(s): We evaluated effectiveness of CB-839, a glutaminase inhibitor, against MCL in in vitro and in vivo preclinical studies. Approach: We employed 1H magnetic resonance spectroscopy (1H MRS) imaging and biochemical analyses to investigate the effects of CB-839 on key metabolites in MCL cells, to potentially identify biomarkers of treatment response. Results: Decreases in lactate and alanine concentration emerged as promising biomarkers of response to CB-839 and may potentially serve as biomarkers in MCL patients. Impact: Therapy-mediated decreased intra-tumoral concentrations of lactate and alanine measured by 1H MRS may potentially become early and sensitive biomarkers of glutaminase inhibition in MCL and, likely, other types of malignancies.