MYC positive + BCL2 positive

However, with larger numbers of DEL cases available in mRNA-based measurement cohorts, there was a statistically significant stratification for PFS (GSE117556: OS, p = 0.084, PFS, p = 0.031; GOYA: OS, p = 0.065, PFS, p = 0.047), suggesting that the following formula refines the current DEL definition and improves its prognostic value: Using a pan-immune protein-marker DSP panel, we identified that the T-cell immune regulators ICOS and 4-1BB were negatively correlated with M+2+6- percentage extent (r = −0.27, p = 0.0046; r = −0.22, p = 0.019, respectively), suggesting a potential role for ICOS or 4-1BB stimulatory therapeutics (e.g. feladilimab, utomilumab) in combination with chemotherapy for high M+2+6- cases. A simple mathematical formula for estimation of MYC+BCL2+BCL6- cells in DLBCL refines the DEL diagnosis, and could be of value in selecting high risk DLBCL for trials of novel agents. High M+2+6- DLBCL display unique T-cell infiltrates, and immunomodulation by ICOS and 4-1BB agonists could represent a therapeutic vulnerability for this high-risk subgroup.

Introduction ‘Double Expressor Lymphomas’ (DEL) refer to Diffuse Large B-Cell Lymphomas (DLBCL) which are positive for MYC and BCL2 by immunohistochemistry (IHC); and have poorer outcomes on standard R-CHOP therapy...Conclusions By investigating single-cell resolved MYC, BCL2 and BCL6 co-expression in DLBCL we have identified a sub-population that robustly predicts prognosis and can refine the traditional definition of DEL. The mathematical model for estimating sub-clonal co-expression from individual oncogene expression data may be applicable to studies of prognostic markers in multiple cancer types.

Introduction: ‘Double Expressor Lymphomas’ (DEL) refer to Diffuse Large B-Cell Lymphomas (DLBCL) which are positive for MYC and BCL2 by immunohistochemistry (IHC); and have poorer outcomes on standard R-CHOP therapy... By investigating single-cell resolved MYC, BCL2 and BCL6 co-expression in DLBCL we have identified a sub-population that robustly predicts prognosis and can refine the traditional definition of DEL. The mathematical model for estimating sub-clonal co-expression from individual oncogene expression data may be applicable to studies of prognostic markers in multiple cancer types.