Glutamine-Derived 2-Hydroxyglutarate Is Associated with Disease Progression in Plasma Cell Malignancies

Gonsalves, W.I.; Ramakrishnan, V.; Hitosugi, T.; et al.

To better understand the clinical significance of 2-hydroxyglutarate (2-HG) in its progression of plasma cell malignancies, Gonsalves and colleagues investigated the production and flux of TCA cycle metabolites in various cell and tissue analyses. The quantitative assessments were facilitated by a stable isotope-resolved metabolomics (SIRM) approach that utilized U-¹³C standards and MS-based methodologies. This study revealed that 2-HG is produced from clonal plasma cells (PCs) and is detectable in the peripheral blood and bone marrow plasma of patients with PC disorders. Also observed was evidence for the exclusive production of 2-HG from glutamine metabolism that appears to be correlated with c-Myc upregulation. This is a clinically significant finding considering the functional link of 2-HG with multiple myeloma that has the potential to be exploited as a decision factor in therapy initiation.