Single Nucleotide Variants and Epimutations Induce Proteasome Inhibitor Resistance in Multiple Myeloma.

Larissa Haertle Santiago Barrio Umair Munawar Seungbin Han Xiang Zhou Michal Simicek Cornelia Vogt Marietta Truger Rafael Alonso Fernández Maximilian Johannes Steinhardt Julia Weingart Renata Snaurova Silvia Nerreter Eva Teufel Andoni Garitano-Trojaola Matteo Claudio Da Via Yanira Ruiz-Heredia Andreas Rosenwald Niccolo' Bolli Roman Hájek Peter Raab Marc-Steffen Raab Niels Weinhold Claudia Haferlach Thomas Haaf Joaquin Martinez Lopez Hermann Einsele Leo Rasche Klaus Martin Kortüm

Published in: Clinical cancer research : an official journal of the American Association for Cancer Research (2022)

Under the selective pressure of PI treatment, MM cells acquire methylation of the PSMD5 promoter silencing the PSMD5 gene expression. PSMD5 acts as a key orchestrator of proteasome assembly and its downregulation was described to increase the cell's proteolytic capacity. PSMD5 hypermethylation, therefore, represents a novel mechanism of PI tolerance in Multiple Myeloma.

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