Promyelocytic leukemia (PML) nuclear bodies are disorganized in colorectal tumors with total loss of major histocompatibility complex class I expression and LMP7 downregulation.

The promyelocytic leukemia (PML) protein is the product of the PML gene that fuses with the retinoic acid receptor-alpha (RARalpha) gene in acute promyelocytic leukemia (APL) and produces disruption of PML bodies. Wild-type PML localizes in the nucleus with a typical speckled pattern. PML bodies accumulate several proteins involved in multiple cellular pathways such as apoptosis, transcriptional regulation, and proteasomal degradation of ubiquitinated proteins. The ubiquitin-proteasome pathway at PML bodies is dependent on proteasome component recruitment. Proteasome components such as low-molecular weight proteins (LMPs) are frequently downregulated in different tumor tissues that present impaired major histocompatibility complex (MHC) class I expression. We have recently documented LMP7 downregulation in colorectal tumors with total loss of MHC class I antigen. An immunohistochemical study of PML protein in these tumors revealed a disrupted pattern of PML bodies in a nuclear diffuse form, as observed in APL cells. Therefore, the disruption of the PML bodies was clearly associated with LMP7 downregulation.