MYC and Metabolomics: Can We Use What We Know for DLBCL Subtyping and Diagnosis?

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a molecular and clinical heterogenous entity, and, over the past 30 years, many efforts have been made in trying to dissect this diverseness and identify biomarkers capable of efficiently stratifying DLBCL patients and spotting the ones showing a worse clinical outcome. Despite the achievement in this research field, only a few biomarkers have been validated and introduced in a clinical setting. Among those, approximately 5-15% of DLBCL cases harbor MYC gene translocations, often involving immunoglobulin genes as a translocation partner, and concomitant point mutations, correlating with a poor response to standard therapies. However, given the difficulty in detecting these abnormalities requiring specialized techniques and high-quality specimens, the use of metabolomics (i.e., the study of small metabolites in body fluids and tissues) can offer a useful alternative for the identification of high-risk DLBCL patients. Amino acids (AAs) are metabolites essential in the process of tumorigenesis and can increase immune escape and drug resistance. Therefore, we review the use of metabolomics to improve the diagnosis and prognosis in DLBCL patients in relation to the MYC role in the regulation of amino acid metabolism, as these metabolites may be used as potential biomarkers in a clinical environment.