The JAK2 inhibitor TG101209 exhibits anti-tumor and chemotherapeutic sensitizing effects on Burkitt lymphoma cells by inhibiting the JAK2/STAT3/c-MYB signaling axis

Yang Zhang; Ji Li; Haiying Zhong; Xiang Xiao; Zhihua Wang; Zhao Cheng; Cunhong Hu; Guangsen Zhang; Sufang Liu

doi:10.1038/s41420-021-00655-1

The JAK2 inhibitor TG101209 exhibits anti-tumor and chemotherapeutic sensitizing effects on Burkitt lymphoma cells by inhibiting the JAK2/STAT3/c-MYB signaling axis

Cell Death Discov. 2021 Sep 29;7(1):268. doi: 10.1038/s41420-021-00655-1.

Authors

Yang Zhang^{1

2

3}, Ji Li^{1

2}, Haiying Zhong^{1

2}, Xiang Xiao^{1

2}, Zhihua Wang^{1

2}, Zhao Cheng^{1

2}, Cunhong Hu^{2

3}, Guangsen Zhang^{1

2}, Sufang Liu^{4

5}

Affiliations

¹ Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
² Institute of Molecular Hematology, Central South University, Changsha, Hunan, 410011, China.
³ Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
⁴ Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. sufang-liu@csu.edu.cn.
⁵ Institute of Molecular Hematology, Central South University, Changsha, Hunan, 410011, China. sufang-liu@csu.edu.cn.

Abstract

Constitutive activation of JAK2/STAT3 is a major oncogenic signaling event involved in the development of Burkitt lymphoma (BL). In the present study, we investigated the antilymphoma activity of TG101209, a specific JAK2 inhibitor, on EBV-positive and EBV-negative Burkitt lymphoma cell lines and primary BL cells. The results showed that TG101209 had a significant antilymphoma effect by inhibiting BL cell growth and inducing apoptosis along with cell differentiation toward mature B cells in vitro. We also found that TG101209 displayed significant synergistic action and a sensitizing effect on the anti-Burkitt lymphoma activity of doxorubicin. In vivo experiments indicated that TG101209 could suppress tumor growth and prolong the overall survival of BL cell-bearing mice. The mechanistic study indicated that TG101209, by suppressing the JAK2/STAT3/c-MYB signaling axis and crosstalk between the downstream signaling pathways, plays an antilymphoma role. These data suggested that TG101209 may be a promising agent or alternative choice for the treatment of BL.

Abstract

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