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

Promyelocytic leukemia (PML) nuclear bodies are important components of nuc lear architecture that are functionally linked to aberrant gene expression and disease. To understand the mechanisms that modify subnuclear distributi on and regulatory activities of PML domains in leukemia, we performed immun ofluorescence microscopy with a panel of normal diploid cells and establish ed 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 spec trum of cell types. The subnuclear organization of PML domains was also eva luated following transient transfection with a series of vectors expressing normal hematopoietic and leukemia related transcription factors. Our resul ts show that expression of a chimeric transcription factor encoded by the t umor related chromosomal translocation (8;21) involving the AML1 and ETO lo ci is sufficient to cause reorganization of PML domains. This finding incre ases 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. (C) 2000 Wiley-Liss, Inc.