Ribosome Profiling Reveals Translational Reprogramming via mTOR Activation in Omacetaxine-Resistant Multiple Myeloma.

ABSTRACT: Protein homeostasis is critical to the survival of multiple myeloma cells. Although this is targeted with proteasome inhibitors, mRNA translation inhibition has not entered trials. Recent work illustrates broad sensitivity of multiple myeloma cells to the translation inhibitor omacetaxine. We hypothesized that understanding how multiple myeloma becomes resistant will lead to the development of drug combinations to prevent or delay relapse. We generated omacetaxine resistance in H929 and MM1S multiple myeloma cell lines and compared them with parental lines. Resistant lines displayed decreased sensitivity to omacetaxine, with EC50 > 100 nmol/L, compared with parental sensitivity of 24 to 54 nmol/L. As omacetaxine inhibits protein synthesis, we performed both RNA sequencing and ribosome prof

SUBMITTER: Walker ZJ 

PROVIDER: S-EPMC12221815 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature