In MLL1-r leukemia, chromosome translocations produce an oncogenic fusion protein consisting of the N-terminal DNA-interacting domains of MLL1 (~ 1400 residues) fused with one of > 70 fusion partner proteins (Fig. 1a) [12–14], among which transcription cofactors AF9 and its paralog ENL, AF4 (also known as AFF1) and its paralog AFF4, and ELL are found in > 70% MLL1-r leukemias (Fig. 1b) [10, 38]. Here, AFF1 is linked to leukemia.