MALT1 Inhibition as a Therapeutic Strategy in T-Cell Acute Lymphoblastic Leukemia by Blocking Notch1-Induced NF-κB Activation
| Autor: | Rong Wang, Huihui Zhang, Jiawen Xu, Ninghan Zhang, Ting Pan, Xiaomin Zhong, Huanxin Zhang, Lingling Yin, Yao Yao, Qingyun Wu, Zhenyu Li, Xuejiao Liu, Kailin Xu, Mingshan Niu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research T cell Chromosomal translocation lcsh:RC254-282 NF-κB 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Original Research Notch1 business.industry Cell growth MALT1 Combination chemotherapy medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Lymphoma 030104 developmental biology medicine.anatomical_structure Oncology chemistry Apoptosis 030220 oncology & carcinogenesis Cancer research business T-ALL MI-2 |
| Zdroj: | Frontiers in Oncology, Vol 10 (2020) Frontiers in Oncology |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|