Taken together, our results suggest PSMC2 overexpression correlates with reduced OS in MM patients treated with bortezomib and that PSMC2 may represent an actionable therapeutic target to prevent or overcome PI resistance. PSMC2 overexpression increases proteasome activity in MM cells, mitigates ER stress on PI challenge and promotes PI resistance.

We interrogated gene expression profiles (GEP) from the randomized, phase 3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) study that compared BTZ with high-dose dexamethasone (DEX) in RRMM patients....Using the CoMMpass database, increased PSMC2 expression also correlated with a worse OS (Figure 1B), while increased PSMC6 correlated with worse OS as well as progression free survival (PFS) (OS- HR= 2.29 p=0.0014, PFS- HR=1.63 p=0.0109)....Taken together, our results indicate that increased PSMC2 and PSMC6 correlates with OS in MM in both patients treated with BTZ in the APEX and with a variety of standard therapies in the CoMMpass database.