In the current study, we report that Aurora A inhibitor shows synergistic effect with BTZ on t(4;14) positive MM cells, and reveal a previously not discovered positive regulating loop between phosphorylation of NSD2 and methylation of Aurora A. Thus, the t(4;14) translocation rendering high level of NSD2 could be used as a hallmark for accessing application of MLN8237 with BTZ based therapy regimen in this subtype of MM patients in order to achieve higher response rate and overcome relapse and refractory. This evidence concerns the gene NSD2 and Miyoshi myopathy.