Mechanistically, whereas wild-type Blimp-1 metabolism is triggered in the nucleus through PML-mediated sumoylation, the degradation of lymphoma-associated mutants is accelerated by subversion of this pathway to Hrd1-mediated cytoplasmic sequestration and ubiquitination.
BLIMP1 is frequently inactivated in a variety of lymphomas, including diffuse large B cell lymphomas, Natural Killer cell lymphoma and anaplastic large T cell lymphoma.
In vivo genomic footprinting of the PRDM1 promoter in unstimulated lymphoma and myeloma cells reveals multiple common in vivo occupied elements throughout the promoter.
PRDM1 protein expression was recently demonstrated in a subset of diffuse large B-cell lymphoma (DLBCL) with aggressive behavior, a type of lymphoma for which rituximab associated with chemotherapy (R-CHOP) is now widely indicated.