4
0This research identifies seven molecularly distinct proteogenotypes (PGs) of diffuse large B cell lymphoma (DLBCL) by integrating proteomic, transcriptomic, and genomic data. While traditional subtyping focuses on genetic mutations or cell-of-origin, this integrated multi-omic approach reveals shared oncogenic pathways and microenvironment features that explain clinical heterogeneity more accurately. A primary finding is the identification of PG4, a high-risk group associated with poor R-CHOP therapy outcomes and a unique biological signature of enhanced MYC activity and T cell exhaustion. The study demonstrates that BTG1 mutations and deregulated TCF3/4 transcriptional activity drive the aggressive nature of PG4 across different genetic backgrounds. Ultimately, these findings establish a new diagnostic framework for identifying refractory cases and provide potential biological targets for future therapeutic intervention.
References:
Enssle J C, Häupl B, Qoku A, et al. Pathogenesis of diffuse large B cell lymphoma proteogenotypes[J]. Cancer Cell, 2026.
