Combination of artesunate and ruxolitinib inhibits T-lymphoblastic leukemia/lymphoma proliferation via the Janus kinase/signal transducer and activator of transcription pathway

Abstract BACKGROUND T-lymphoblastic leukemia/lymphoma is a highly aggressive malignancy, and its prognosis after relapse is poor, with a 5-year overall survival rate of 35%. Mutations in the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway are the second most common mutation type in T-lymphoblastic leukemia/lymphoma, and hyperactivation of this pathway can promote tumor proliferation. Because artesunate and ruxolitinib can inhibit JAK/STAT pathway activation, this study investigated the utility of these drugs in the treatment of T-lymphoblastic leukemia/lymphoma. METHODS Jurkat cells were treated with different concentrations of artesunate and/or ruxolitinib. Cell viability was detected by the CCK-8 assay, and apoptosis was detected after 48 h of treatment using flow cytometry. The effect of the drugs alone and in combination on the JAK/STAT pathway in Jurkat cells was analyzed by PCR and western blotting. In addition, the expression of relevant JAK/STAT pathway proteins in the lymph nodes of patients with T-lymphoblastic leukemia/lymphoma was analyzed. RESULTS Artesunate and ruxolitinib, both alone and in combination, promoted apoptosis and reduced JAK2 and STAT5 phosphorylation, but the mRNA or protein expression of JAK2 and STAT3 was not altered. The drugs in combination had a stronger growth-inhibitory effect than either drug alone. CONCLUSION Artesunate and ruxolitinib alone and in combination inhibited the aberrant activation of the JAK/STAT pathway in T lymphoma/leukemia, supporting the utility of this combination in patients with JAK/STAT protein mutations.