Getting to the root of the problem: the causes of relapse in multiple myeloma

Multiple myeloma (MM) remains incurable, and ultimately, patients exhibit disease progression under current treatment regimens. Proteasome inhibitors have emerged as frontline treatment of relapsed and refractory MM however, resistance to these drugs occur through poorly defined mechanisms. Numerous studies have identified different acquired resistance models such as beta 5 proteasome subunit mutations and stabilization of tumor suppressors and apoptotic proteins. In addition, recent findings have identified a progenitor organization in MM whereby early progenitor tumor cells show resistance to proteasome inhibitor therapy and cause progressive disease with maturation arrest. This editorial highlights the potential causes of MM relapse in the context of these tumor progenitor cells and the role these cells play in treatment failure.