The metabolism of lymphomas

Abstract

Purpose of review: Cellular to animal to human studies are shedding light on metabolic pathways that contribute to sustaining lymphomagenesis. Old players with new metabolic tricks and new metabolic players come into the scene. The purpose of this review is to discuss the recent advances made in the field of lymphoma metabolism with special focus on the metabolic modulation of tumor promoting and suppressing pathways and, conversely, on the effect of these pathways on metabolite addiction.

Recent findings: The basis for the high glucose uptake and glycolytic activity in lymphoma cells is now beginning to be understood. Recent findings suggest a greater role of nucleotide biosynthesis as a major driving force for glycolysis, especially during proliferation and cellular stress conditions. There is new evidence for an increasing contribution of glycine-folate metabolism deregulation in nucleotide biosynthesis, genome integrity and epigenetic maintenance. Expanding roles for MYC, PI3K and TP53 in regulating reactive oxygen production, glycolysis and glutaminolysis in lymphoma cells have been described. The identification of novel pathways has allowed the emergence of new 'antimetabolite' strategies to increase the therapeutic efficacy of current approaches.

Summary: Metabolism in lymphomas must fulfill the general demands from cell proliferation and those specific to lymphomagenesis. Data emerging from preclinical studies are elucidating the metabolic pathways that contribute to maintaining the malignant phenotype in lymphomas. This has resulted in identification of novel pathways, some of which may have a clinical impact in the diagnosis, characterization and treatment of lymphoma subtypes.