The role of phase separation by NUP98 fusion oncoproteins in leukemia

NUP98 fusion oncoproteins (FOs) are hallmarks of high-risk acute leukemia in children. NUP98 FOs universally contain the intrinsically disordered N-terminal region of NUP98, which harbors multiple “sticky” phenylalanine-glycine (FG) motifs. NUP98 fusion partners include a diverse set of genes that predominantly encode transcriptional or epigenetic regulators bearing folded DNA or chromatin-binding domains. Here, we focused on NUP98-HOXA9 (NHX9), an FO linking the N-terminal FG repeat domains of NUP98 (NUP98-FG) and the DNA-binding homeodomain (HD) of HOXA9.