Effects on gene expression of nuclear export inhibitor in control and TP53-knockdown cell line of mantle cell lymphoma

The TP53 wild-type cell line JVM2, representing mantle cell lymphoma (MCL), was transduced to create control or TP53 knockdown (KD) forms. These were then either left untreated or treated with KPT-185, a selective inhibitor of nuclear export (SINE) by XPO1, for gene expression profiling (GEP). Consistent with the observation that KPT-185 was equally toxic to both forms, the majority of gene expression changes resulting from KPT-185 treatment were similar for both forms, even though TP53 is known to be one of the cargo proteins of XPO1. GEP showed downregulation of genes involved in proliferation, consistent with findings of cell cycle analysis and supported by Western blot results. Quantitative proteomics revealed repression of ribosomal biogenesis to be a major TP53-independent effect of KPT-185. GEP data were used for comparison to similarly-prepared B-cell depleted fractions of follicular lymphoma samples.