Metabolic Reprogramming in Lymphoma Cells

Lymphoma cells undergo profound shifts in their energy pathways to support rapid proliferation, survival under stress and resistance to therapy. These shifts encompass enhanced glucose uptake and aerobic glycolysis (the Warburg effect), increased mitochondrial oxidative phosphorylation, elevated glutamine metabolism and augmented fatty acid synthesis or oxidation. Genetic and epigenetic alterations in oncogenes and tumour suppressors converge on master regulators such as mTOR and MYC to drive this reprogramming. In parallel, the tumour microenvironment contributes reactive oxygen species and inflammatory cues that further reshape metabolic fluxes. The net result is the accumulation of oncometabolites, dynamic substrate flexibility and rewiring of signalling–metabolism crosstalk. A detailed understanding of these interlinked pathways has highlighted metabolic enzymes and metabolites as potential biomarkers and therapeutic vulnerabilities in B-cell and T-cell lymphomas worldwide.

Research from Nature Portfolio

One foundational study demonstrated that fatty acid synthase (FASN) not only fuels lipid production in diffuse large B-cell lymphoma but also engages PI3K–S6Kinase signalling to activate the deubiquitinase USP11. This enzyme stabilises the translation factor eIF4B, thereby sustaining global oncogenic protein synthesis. Pharmacological or genetic inhibition of FASN disrupted this axis, leading to diminished eIF4B levels, reduced translational output and impaired lymphoma cell growth. This work revealed a direct link between lipid metabolism and dysregulated translation machinery, suggesting combined metabolic and translational targeting as a promising strategy in aggressive lymphomas.

Metabolic Reprogramming in Lymphoma Cells publication trend

The graph below shows the total number of articles in metabolic reprogramming in lymphoma cells across all publications each year (not limited to Nature Index journals).

Technical terms

Warburg effect: Preference of cancer cells for aerobic glycolysis over oxidative phosphorylation, even in the presence of oxygen.

Oncometabolite: A metabolite whose accumulation promotes oncogenic signalling, epigenetic changes or tumour progression.

Glutaminolysis: Metabolic conversion of glutamine into tricarboxylic acid cycle intermediates to support bioenergetics and anabolism.

Fatty acid oxidation: Mitochondrial breakdown of fatty acids into acetyl-CoA for energy production.

eIF4B: Eukaryotic initiation factor critical for ribosomal recruitment and initiation of mRNA translation in protein synthesis.

References

1. Oxidative Stress and Inflammation in B-Cell Lymphomas. Antioxidants (2023).
2. Metabolic Reprogramming and Potential Therapeutic Targets in Lymphoma. International Journal of Molecular Sciences (2023).
3. Disturbed Plasma Lipidomic Profiles in Females with Diffuse Large B-Cell Lymphoma: A Pilot Study. Cancers (2023).
4. Fatty Acid Synthase induced S6Kinase facilitates USP11-eIF4B complex formation for sustained oncogenic translation in DLBCL. Nature Communications (2018).