Proteasomal adaptations underlying carfilzomib-resistance in human bone marrow plasma cells.

ABSTRACT: Donor-specific antibodies (DSAs) have a deleterious effect on allografts and remain a major immunologic barrier in transplantation. Current therapies to eliminate DSAs are ineffective in highly HLA-sensitized patients. Proteasome inhibitors have been employed as a strategy to target bone marrow plasma cells (BMPCs), the source of long-term antibody production; however, their efficacy has been limited by poorly defined drug-resistance mechanisms. Here, we performed transcriptomic profiling of CD138⁺ BMPCs that survived in vivo desensitization therapy with the proteasome inhibitor carfilzomib to identify mechanisms of drug resistance. The results revealed a genomic signature that included increased expression of the immunoproteasome, a highly specialized proteasomal variant. Weste

SUBMITTER: Woodle ES 

PROVIDER: S-EPMC6984988 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature