Genetic Alterations in Members of the Proteasome 26S Subunit, AAA-ATPase (<i>PSMC</i>) Gene Family in the Light of Proteasome Inhibitor Resistance in Multiple Myeloma.

ABSTRACT: For the treatment of Multiple Myeloma, proteasome inhibitors are highly efficient and widely used, but resistance is a major obstacle to successful therapy. Several underlying mechanisms have been proposed but were only reported for a minority of resistant patients. The proteasome is a large and complex machinery. Here, we focus on the AAA ATPases of the 19S proteasome regulator (PSMC1-6) and their implication in PI resistance. As an example of cancer evolution and the acquisition of resistance, we conducted an in-depth analysis of an index patient by applying FISH, WES, and immunoglobulin-rearrangement sequencing in serial samples, starting from MGUS to newly diagnosed Multiple Myeloma to a PI-resistant relapse. The WES analysis uncovered an acquired PSMC2 Y429S mutation at the rel

SUBMITTER: Haertle L 

PROVIDER: S-EPMC9856285 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature