AFF1 and acute lymphoblastic leukemia: ALL with rearrangements of the KMT2A gene (formerly MLL) cause in-frame gene fusions creating novel fusion proteins.18 The most common KMT2A rearrangement is KMT2A::AFF1,18 which is the major cause of infant ALL and, relative to other subtypes, has a low mutational burden and no common cooperating mutations.