The first evidence linking NSD1 genetic aberrations to cancer came from cloning of a cytogenetically silent t(5;11)(q35;115) chromosomal translocation associated with pediatric de novo MDS or aggressive AML that leads to fusion of the N-terminal domains of the nucleopore 98 (NUP98) protein to the C-terminal part (including the SET) of NSD1 [56]. The gene discussed is NUP98; the disease is acute myeloid leukemia.