Exportin 1‐mediated nuclear/cytoplasmic trafficking controls drug sensitivity of classical Hodgkin's lymphoma

The XPO1 gene controls the subcellular trafficking of regulatory proteins and is overexpressed in various cancers. Small inhibitors of nuclear export (SINEs) have been developed to inhibit XPO1. In PMBL and cHL, the XPO1 gene may be mutated, resulting in mutant XPO1E571K. Mutant XPO1 leads to a faster degradation of the protein and renders lymphoma cells more sensitive to SINEs like selinexor. The mutation also affects the trafficking of transcription factors p65 and p52 between the nuclear and cytoplasmic compartments, which accounts for the response towards the drug ibrutinib. XPO1 mutation could be used as a biomarker to predict the response of PMBL and cHL cells to SINEs and drugs that target the NFκB signaling pathway.