Comprehensive Metaboproteomics of Burkitt’s and Diffuse Large B‑Cell Lymphoma Cell Lines and Primary Tumor Tissues Reveals Distinct Differences in Pyruvate Content and Metabolism

Burkitt’s
lymphoma (BL) and diffuse large B-cell lymphoma
(DLBCL) are pathologically and clinically distinct subtypes of aggressive
non-Hodgkin B-cell lymphoma. To learn more about their biology, we
employed metabolomic and proteomic methods to study both established
cell lines as well as cryopreserved and formalin-fixed paraffin-embedded
(FFPE) tissue sections of BL and DLBCL. Strikingly, NMR analyses revealed
DLBCL cell lines to produce and secrete significantly (padj = 1.72 × 10–22) more pyruvic
acid than BL cell lines. This finding could be reproduced by targeted
GC/MS analyses of cryopreserved tissue sections of BL and DLBCL cases.
Enrichment analysis of an overlapping set of N =
2315 proteins, that had been quantified by nanoLC–SWATH-MS
in BL and DLBCL cultured cells and cryosections, supported the observed
difference in pyruvic acid content, as glycolysis and pyruvate metabolism
were downregulated, while one-carbon metabolism was upregulated in
BL compared to DLBCL. Furthermore, 92.1% of the overlapping significant
proteins showed the same direction of regulation in cryopreserved
and FFPE material. Proteome data are available via ProteomeXchange
with identifier PXD004936.