Comprehensive gene expression profiles of NK cell neoplasms identify vorinostat as an effective drug candidate

NK cell neoplasms are lymphoid malignancies with an aggressive clinical course. In the present study, we analyzed gene expression profiling of NK cell neoplasms and attempted to identify important molecular pathways and new effective drugs. Pathway analysis of gene expression profiles suggested the important roles of the JAK-STAT pathway, NF-κB pathway or Wnt pathways in NK cell neoplasms. Notably, western blot analysis revealed that STAT3 was expressed and phosphorylated at a higher level in NK cell lines than in normal NK cells or other cell lines. These findings indicate the occurrence of JAK-STAT activation in NK cell neoplasms. Connectivity Map (CMAP) analysis of gene expression profiles identified candidate drugs against NK cell neoplasms. Among the drugs suggested by CMAP analysis, we focused on puromycin, phenoxybenzamine, LY294002, wortmannin, vorinostat and trichostatin A because they exhibited high enrichment scores. We added these drugs to NK cell lines and other cell lines. Among the drugs, vorinostat suppressed NK cell line proliferation at a significantly lower concentration compared to other cell lines. Suppression of the JAK-STAT pathway appeared to contribute to this effect. Vorinostat may be a good candidate for use in the therapy against NK cell neoplasms.

► Pathway analysis suggested the important roles of the JAK-STAT, NF-κB and Wnt pathways in NK cell neoplasms. ► Connectivity Map analysis suggested vorinostat as one of candidate drugs against NK cell neoplasms. ► Vorinostat suppressed NK cell line proliferation at a significantly lower concentration compared to other cell lines. ► Vorinostat may be a good candidate for use in the therapy against NK cell neoplasms.