Use of ATRA for acute promyelocytic leukemia (APL) is considered the first example of modern targeted cancer therapy23, 24, 25, 26, 27, but how it causes driven fusion oncogene PML–RAR-α degradation and inhibition of self-renewal of leukemia stem cells had remained elusive28, 29. Here, RARA is linked to acute promyelocytic leukemia.