Leukemia-associated AML1/ETO (8;21) chromosomal translocation protein increases the cellular representation of PML...

Promyelocytic leukemia (PML) nuclear bodies are important components of nuclear architecture that are functionally linked to aberrant gene expression and disease. To understand the mechanisms that modify subnuclear distribution and regulatory activities of PML domains in leukemia, we performed immunofluorescence microscopy with a panel of normal diploid cells and established cell lines. We analyzed the representation and intranuclear distribution of PML domains. We find that multiple biological parameters contribute to heterogeneity in the subnuclear organization of PML domains in a broad spectrum of cell types. The subnuclear organization of PML domains was also evaluated following transient transfection with a series of vectors expressing normal hematopoietic and leukemia-related transcription factors. Our results show that expression of a chimeric transcription factor encoded by the tumor related chromosomal translocation (8;21) involving the AML1 and ETO loci is sufficient to cause reorganization of PML domains. This finding increases our understanding of the mechanisms by which the AML1/ETO protein may contribute to modified gene expression linked to the onset and progression of t(8;21) related acute myelogenous leukemia.