KMT2A and leukemia: On the surface, the combination of BCR–ABL1 fusion and loss of IKZF1 neatly fits the paradigm proposed by Gilliand for acute myeloid leukemia (AML), which hypothesized that leukemia development requires a combination of class I (signal transduction pathway mutation leading to uncontrolled growth, such as FLT3, or RAS), and class II mutations (aberrant transcription factors resulting in differentiation block, such as PML–RAR, AML–ETO, MLL-translocations, or point mutations in C/EBPα) (111).