Delayed CR (that is, CR after 35 days of therapy) has been associated with a higher rate of relapse (31% vs 17%, P=0.001).73 Failure to achieve remission after ATRA-based induction therapy is rare, largely restricted to rare patients with ATRA-resistant variants, such as PLZF-RARA-positive APL.74 Resistance to ATO has recently been described in a series of 13 ATO-resistant APL patients using direct sequencing, 9 of whom harbored PML mutations, and 7 of these simultaneously harbored RARA mutations.75 Here, RARA is linked to acute promyelocytic leukemia.