To mimic SAG deletion, we used MLN4924, a newly discovered small molecule inhibitor of NAE [35] that inactivates SAG-SCF E3 ligase by blocking cullin neddylation [35], [42], and found that combination of RA and MLN4924 caused significantly more apoptosis than each drug alone in two RA resistant AML cell lines. The gene discussed is CACUL1; the disease is acute myeloid leukemia.