Highlighting the importance of tissue distribution of differently composed γ-secretase complexes, GSI MRK-560 had higher affinity to PSEN1 than to PSEN2-containing GS complex providing a strategy to selectively inhibit GS of T-ALL cells, expressing only PSEN1 without affecting the physiological function of Notch in the gastrointestinal tract, where PSEN2 compensated the lacking activity of PSEN1 (Table S1) [169]. Here, PSEN1 is linked to acute lymphoblastic leukemia.