Taken together, our study provides compelling evidence that GSPT1 degradation leads to a strong anti-proliferative effect in RUNX1::RUNX1T1 AML subgroup and to the corresponding degradation of the RUNX1::RUNX1T1 fusion protein, as well as a robust antiproliferative activity in the high-risk FUS::ERG AML subgroup. Here, RUNX1 is linked to acute myeloid leukemia.