Posttranslational modification of Aurora A-NSD2 loop contributes to drug resistance in t(4;14) multiple myeloma.

ABSTRACT:

Background

t(4;14)(p16;q32) cytogenetic abnormality renders high level of histone methyltransferase NSD2 in multiple myeloma (MM) patients, and predicts poor clinical prognosis, but mechanisms of NSD2 in promoting chemoresistance have not been well elucidated.

Methods

An epigenetics compound library containing 181 compounds was used to screen inhibitors possessing a prior synergistic effect with bortezomib (BTZ) in vitro. Molecular biology techniques were applied to uncover underlying mechanisms. Transcriptome profile assay was performed by RNA-seq. NSG mouse-based xenograft model and intra-bone model were applied to qualify the synergistic effect in vivo.

Results

We identified an Aurora kinase A inhibitor (MLN8237) possessed a significant synergistic effect with BTZ

SUBMITTER: Jiang H 

PROVIDER: S-EPMC8989081 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature