RNA-seq enabled the discovery of novel genomically defined ALL subtypes, characterized by chromosomal rearrangements cryptic on karyotyping (e.g., DUX4-rearranged ALL), new fusion genes (e.g., MEF2D, ZNF384, or NUTM1-R ALL) and expression profiles similar to classic BCP-ALL subtypes, e.g., BCR-ABL-like, ETV6-RUNX1-like [6,7]. Here, DUX4 is linked to acute lymphoblastic leukemia.