AFF1 and acute lymphoblastic leukemia: Although activation of the unfolded protein response (UPR) has been reported at a specific stage of B-cell development35 and sensitivity of primary ALL cells to PIs was correlated with high basal levels of ER stress11, alternative mechanisms have also been proposed for cells that express the KMT2A::AFF1 fusion protein and are highly sensitive to Btz36,37.