Metabolic Biomarkers in B-Cell Lymphomas for Early Diagnosis and Prediction, as Well as Their Influence on Prognosis and Treatment

Abstract

B-cell lymphomas exhibit a vast variety of clinical and histological characteristics that might complicate the diagnosis. Timely diagnosis is crucial, as treatments for aggressive subtypes are considered successful and frequently curative, whereas indolent B-cell lymphomas are incurable and often need several therapies. The purpose of this review is to explore the current advancements achieved in B-cell lymphomas metabolism and how these indicators help to early detect metabolic changes in B-cell lymphomas and the use of predictive biological markers in refractory or relapsed disease. Since the year 1920, the Warburg effect has been known as an integral part of metabolic reprogramming. Compared to normal cells, cancerous cells require more glucose. These cancer cells undergo aerobic glycolysis instead of oxidative phosphorylation to metabolize glucose and form lactate as an end product. With the help of these metabolic alterations, a novel biomass is generated by the formation of various precursors. An aggressive metabolic phenotype is an aerobic glycolysis that has the advantage of producing high-rate ATP and preparing the biomass for the amino acid, as well as fatty acid, synthesis needed for a rapid proliferation of cells, while aerobic glycolysis is commonly thought to be the dominant metabolism in cancer cells. Later on, many metabolic biomarkers, such as increased levels of lactate dehydrogenase (LDH), plasma lactate, and deficiency of thiamine in B-cell lymphoma patients, were discovered. Various kinds of molecules can be used as biomarkers, such as genes, proteins, or hormones, because they all refer to body health. Here, we focus only on significant metabolic biomarkers in B-cell lymphomas. In conclusion, many metabolic biomarkers have been shown to have clinical validity, but many others have not been subjected to extensive testing to demonstrate their clinical usefulness in B-cell lymphoma. Furthermore, they play an essential role in the discovery of new therapeutic targets.

Absolute Metabolite Quantification Using Pure Shift NMR: Toward Quantitative Metabolic Profiling of Aqueous Biological Samples

“…We are now in a position to analyze accurately the changes in metabolite concentrations between CT and MD samples. It is, for instance, clear that the growth of DLBCL cells has reduced the concentration in Glc, in Gln, and in Ala, which are three key players in the metabolism of DLBCL cell lines . Conversely, DLBCL has secreted Lac, which is a metabolic product known to be produced in large quantities due to the high metabolic rate and reprograming in cancer cells .…”

“…It is, for instance, clear that the growth of DLBCL cells has reduced the concentration in Glc, in Gln, and in Ala, which are three key players in the metabolism of DLBCL cell lines. 36 Conversely, DLBCL has secreted Lac, which is a metabolic product known to be produced in large quantities due to the high metabolic rate and reprograming in cancer cells. 37 Interestingly, we also observed a production of Glu that arises at least in part from the consumption of Gln, this conversion being a key metabolic pathways in DLBCL.…”

Comparison of serum sIL-2R and LDH levels in patients with intravascular large B-cell lymphoma and patients with advanced stage diffuse large B-cell lymphoma

“…The LDH levels are significantly higher in patients with aggressive B-cell lymphoma and can be used as a screening tool to determine the response of a particular treatment or its recurrence. 18 Tumor lysis occurs in both IVL and DLBCL, NOS, but in the case of IVL, it occurs intravascularly and might be acutely reflected in laboratory values. It may also be possible that in tumor cells decay is more likely to occur when tumor cells are in the blood vessels than when they are present as a mass, and that tumor proliferation and destruction may be occurring at a faster rate in IVL, resulting in higher LDH levels.…”

Current Status of Novel Agents for the Treatment of B Cell Malignancies: What’s Coming Next?

“…Metabolomic approaches on plasma of patients with B cell malignancies may allow to identify metabolic biomarkers for early diagnosis and prediction, prognosis and treatment [ 409 ]. Although many metabolic biomarkers have already shown their clinical validity, many others have not yet been subjected to extensive testing to demonstrate their clinical usefulness in B-cell malignancies.…”