Combination Lenalidomide/Bortezomib Treatment Synergistically Induces Calpain-Dependent Ikaros Cleavage and Apoptosis in Myeloma Cells.

ABSTRACT: Multiple myeloma had been successfully treated by combining lenalidomide and bortezomib with reports suggesting benefits of such a combination even in relapsed/refractory cases. Recently, it was demonstrated that Ikaros degradation by lenalidomide happens via proteasome-dependent pathway and this process is critical for the eradication of myeloma cells. On the basis of this, an antagonistic effect should be observed if a combination of both these agents were used, which however is not the observation seen in the clinical setting. Our study demonstrates that when these agents are combined they exhibit a synergistic activity against myeloma cells and degradation of Ikaros happens by a proteasome-independent calcium-induced calpain pathway. Our study identifies the crucial role of calcium-ind

SUBMITTER: Ganesan S 

PROVIDER: S-EPMC7115922 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature