AFF1 and acute lymphoblastic leukemia: These KMT2A rearrangements are responsible for ~75% of acute leukemias (AML, acute lymphoblastic leukemia/ALL, and mixed-lineage leukemia/MLL) in infants and up to 10% in children and adults, and are also found in therapy-related AML.8,12 During KMT2A rearrangement, the C-terminal SET domain is replaced with one of several different fusion partner proteins, which are most frequently transcription co-factor proteins such as AFF1 (AF4), MLLT3 (AF9), MLLT10 (AF10), MLLT1 (ENL), or ELL.