Trends Immunol. 2025 Nov 7:S1471-4906(25)00251-0. doi: 10.1016/j.it.2025.10.007. Online ahead of print.
ABSTRACT
Germinal center B cell-like diffuse large B cell lymphoma (GCB-DLBCL) originates from the malignant transformation of germinal center B cells. This process is driven by transcriptional and epigenetic dysregulations, frequently caused by recurrent mutations and chromosomal translocations. These changes lead to a differentiation arrest associated with unchecked proliferation and survival. This review highlights key transcriptional and epigenetic dependencies that sustain the GCB-DLBCL phenotype and identifies therapeutic vulnerabilities. Epigenetic targeting of these vulnerabilities unlocks tumor cells from their differentiation arrest, enabling further yet incomplete differentiation toward an antiproliferative, proapoptotic plasma cell-like or memory B cell-like state. We define this transition as an epigenetically programmed identity crisis, a promising therapeutic strategy to target GCB-DLBCL and potentially other malignancies.
PMID:41206331 | DOI:10.1016/j.it.2025.10.007