B cell lymphoma with different metabolic characteristics show distinct sensitivities to metabolic inhibitors

Abstract

Purpose: Cancer cells exhibit profound alterations in their metabolism (abnormal glucose and glutamine metabolism). Targeting cancer metabolism is a promising therapeutic strategy. Lymphoma can be classified into many different types and it is very complicated. Therefore, in this paper, we want to know whether the B cell lymphoma cells with different metabolic characteristics have distinct sensitivities to metabolic inhibitors.Methods: We classified 9 B cell lymphoma cell lines into different metabolic subtypes according to the dependency on glutamine and glucose. Then we detected the OCR, ECAR, glucose consumption and lactate production, mitochondrial content and growth rate. And we also determined the IC50 of these 9 cell lines to metabolic inhibitors.Results: According to the dependency on glutamine and glucose, we successfully classified three distinct metabolic subtypes in B cell lymphoma cell lines, one subtype was defined glutamine and glucose equally utilized subtype (GLN=Glu), whereas the other two subtypes were GLN-addicted and Glu-dependent. And these three subtypes showed striking differences in glucose and glutamine utilization, glycolysis and mitochondrial function, and proliferation rate. GLN-addicted and Glu-dependence subtypes also showed differences in cell sensitivity to inhibitors of glutamine and glycolysis metabolism, respectively. However, GLN=Glu subtype seems minimal sensitive to glycolytic and glutaminolytic inhibitors, and with high proliferation rate.Conclusions: The cells rely more on glucose/gltamine have a stronger sensitivity to glucose/glutamine depletion or glycolysis/ glutaminolysis inhibition and a lessened sensitivity to glutaminolysis/glycolysis inhibitors. To target tumor metabolism based on metabolic characteristics may provide a new therapeutic strategy for the treatment of B cell lymphoma.

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