NAE1 and chronic myelogenous leukemia, BCR-ABL1 positive: On the basis of the finding that the NEDD8-activating enzyme subunit NAE1 is overexpressed in CML cells, the NAE1 inhibitor MLN4924 was also demonstrated to induce G2-M arrest and apoptosis in CML cells, regardless of their T315I mutation status in Bcr-Abl, which offers a preclinical proof of concept for targeting protein neddylation as a novel therapeutic strategy to override mutation-derived imatinib resistance in CML [68].