Metabolism of lymphocytes and lymphomas

The bioenergetic activity of cells is controlled by the energy (ATP) demand and coordinated by signal transduction pathways and transcription factors that directly modulate nutrient uptake and metabolism. In normal lymphocytes as well as in lymphoma cells, growth-promoting BCR and TCR signaling, PI3K activity and transciption factor activation (e.g. MYC) collectively modulate energy and nutrient metabolism. In turn, metabolic pathways may affect epigenetic gene regulatory mechanisms. In the whole body, metabolic pathway enzymes, such as Cytochrome-P450, glutathione-S-transferase and N-acetyltransferases that are involved in activation and detoxification of chemotherapy drugs play an important role in lymphoma chemosensitivity. Our study of the metabolism of tumors provides information not only on a specific metabolic pathway but is also used to develop surrogate biomarkers of the status of signaling (e.g. PI3K activation), genetic (e.g. IDH, FH mutations) and epigenetic (e.g. DNA methylation) abnormalities that constitute a particular phenotype.