Protein Profiling Identify Distinct Tumor-Tissue Protein Expression Pattern Specific for Relapsing Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. Several genetic drivers have been suggested based on gene-expression and RNA sequencing. However, clinical trials based on these molecular subclassifications have failed to improve treatment results and standard of care in DLBCL is still R-CHOP (rituximab, cyclophosphamide, doxorubicin, prednisone) based therapy, which results in approximately an 70% 5-year overall survival rate. Nordic Lymphoma Group (NLG) has conducted two large phase II trials (NLG-LBC-04; NCT 01502982 and NLG-LBC-05; NCT 01325194) during the last decade with the aim of improving the treatment outcome for young (<65 years) high-risk patients with primary DLBCL. Both protocols were based on biweekly administered R-CHOP-14 with etoposide (R-CHOEP) and systemic central nervous system (CNS) prophylaxis. Various factors acting at different biological levels may influence pathology of the disease, and discrepancies between gene expression and the final combination of the functional proteins may be present due to, e.g., translational inhibition/activation and posttranslational modifications. Mass spectrometry-based protein profiling is a high throughput methodology that enables identification of the proteins in a given cell or tissue and the global protein expression can be compared between patients.