MALT1 Inhibition as a Therapeutic Strategy in T-Cell Acute Lymphoblastic Leukemia by Blocking Notch1-Induced NF-κB Activation
oleh: Rong Wang, Rong Wang, Huihui Zhang, Huihui Zhang, Jiawen Xu, Jiawen Xu, Ninghan Zhang, Ninghan Zhang, Ting Pan, Ting Pan, Xiaomin Zhong, Huanxin Zhang, Lingling Yin, Yao Yao, Qingyun Wu, Qingyun Wu, Zhenyu Li, Zhenyu Li, Xuejiao Liu, Kailin Xu, Kailin Xu, Mingshan Niu, Mingshan Niu
| Format: | Article |
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| Diterbitkan: | Frontiers Media S.A. 2020-09-01 |
Deskripsi
Current treatment of T-cell acute lymphoblastic leukemia (T-ALL) is primarily based on high-intensity combination chemotherapy, which has serious side effects. Therefore, developments of novel targeted therapeutics are urgently needed for treatment of T-ALL. In this study, we found that mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a novel promising therapeutic target for treatment of T-ALL. MALT1 inhibitor MI-2 significantly suppressed the cell growth, proliferation, and colony formation of T-ALL cells. Furthermore, MI-2 induced cell apoptosis of T-ALL via a mitochondrial-dependent pathway. In a T-ALL mouse model, MI-2 significantly reduced leukemic burden and prolonged the survival of leukemia-bearing mice. Mechanistically, MALT1 inhibition effectively blocked both baseline and Notch1-induced activation of nuclear factor κB pathway, which mediates T-ALL cell survival. In conclusion, our results highlight the potential role of MALT1 as an attractive target for treatment of T-ALL and support the potential of MI-2 or other MALT1 inhibitors to clinical trials in T-ALL.