Combination of artesunate and ruxolitinib suppresses T cell leukemia/lymphoma proliferation via the JAK STAT pathway

TL;DR

Combining artesunate and ruxolitinib can reduce the growth of T-cell leukemia/lymphoma by inhibiting the JAK/STAT pathway.

Contribution

The study demonstrates a novel drug combination that effectively suppresses T-cell leukemia/lymphoma via JAK/STAT pathway inhibition.

Findings

Artesunate and ruxolitinib together significantly increased apoptosis in Jurkat cells.

The combination reduced phosphorylation of JAK2 and STAT5 without affecting their expression.

The drug combination showed stronger anti-proliferative effects than either drug alone.

Abstract

T-cell lymphoblastic leukemia/lymphoma is a highly aggressive malignancy with a 5-year overall survival rate of 35%. Mutations in the JAK/STAT pathway are the second most common mutations in T-cell lymphoblastic leukemia/lymphoma, and hyperactivation of this pathway can promote proliferation of tumor cells. Considering that artesunate and ruxolitinib can inhibit activation of the JAK/STAT pathway, this study investigated the value of these drugs in the treatment of T-lymphoblastic leukemia/lymphoma. Jurkat cells were treated with various concentrations of artesunate and/or ruxolitinib. Cell viability was detected using the CCK-8 assay, and apoptosis was detected after 48 h of treatment using flow cytometry. The effect of each drug alone and in combination was analyzed by polymerase chain reaction and western blotting assays. We also investigated the expression of relevant proteins in the JAK/STAT pathway in lymph nodes and bone marrow samples from 10 patients with T-lymphoblastic leukemia/lymphoma and two healthy controls. Artesunate and ruxolitinib, both alone and in combination, promoted apoptosis and reduced phosphorylation of JAK2 and STAT5 but did not alter mRNA or protein expression of JAK2. The drugs had a stronger inhibitory effect on growth when used in combination than when either was administered alone. Cytotoxicity assays indicated that artesunate had a potent inhibitory effect on cell viability, with IC50 values of 12.86 (24 h) and 5.412 µM (48 h), whereas ruxolitinib had weaker activity (with an IC50 of 30.55 µM at 24 h and 15.51 µM at 48 h). At 24 h, the total apoptotic rate was 20.75% in the control group, 30.00% in the 20 µM artesunate group, 27.24% in the 30 µM ruxolitinib group, and 43.39% in the combination group. Artesunate and ruxolitinib alone and in combination inhibited aberrant activation of the JAK/STAT pathway in T-lymphoblastic lymphoma/leukemia, supporting the value of this combination in patients with JAK/STAT protein mutations.

The online version contains supplementary material available at 10.1038/s41598-026-39393-8.

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