tris(2-pyridylmethyl)amine and Leukemia--Myeloid--Acute

Acute myeloid leukemia (AML) is frequently associated with chromosomal translocations. These translocations produce specific fusion genes that play crucial roles in leukemogenesis. We recently identified a novel NUP98-PHF23 fusion in AML. In this study, we attempt to determine the role of NUP98-PHF23 protein and its plant homeodomain (PHD) and coiled-coil domain in regulation of cellular differentiation and protein distribution. We provide evidence that NUP98-PHF23, through its PHD domain, impairs TPA-induced differentiation of K562 cells. While the fusion protein localizes to the nucleus, its deletion mutant without the PHD domain resides exclusively in the nucleolus, suggesting a potential link between chromatin-binding PHD domain and nuclear architecture.

Topics: Animals; Blotting, Western; Cell Differentiation; Cell Nucleus; Flow Cytometry; Homeodomain Proteins; Humans; K562 Cells; Leukemia, Myeloid, Acute; Mice; NIH 3T3 Cells; Nuclear Pore Complex Proteins; Oncogene Proteins, Fusion; Protein Structure, Tertiary; Pyridines; Sequence Deletion; Translocation, Genetic