Effect of the janus kinase inhibitor ruxolitinib on gene expression of chronic lymphocytic leukemia cells in vivo. Effect of the janus kinase inhibitor ruxolitinib on gene expression of chronic lymphocytic leukemia cells in vivo

Symptomatic previously untreated chronic lymphocytic leukemia patients were treated with the janus kinase (JAK)-inhibitor ruxolitinib (clinicaltrials.gov, number NCT02015208). CLL cells from 6 of the patients were purified prior to commencing ruxolitinib and again 4 or 8 weeks after treatment and analyzed by RNAseq. Ruxolitinib induced a stereotyped response in all patients consisting of a rapid decrease in palpable lymphadenopathy accompanied by increased lymphocytosis and blood lactate dehydrogenase. This response was associated with evidence of inhibited JAK-signaling in CLL cells but activation of other oncogenic pathways. Overall design: Gene expression in circulating CLL cells before and 4-8 weeks after treatment with ruxolitinib were compared by RNAseq.