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MALT1 Inhibition as a Therapeutic Strategy in T-Cell Acute Lymphoblastic Leukemia by Blocking Notch1-Induced NF-κB Activation.
- Source :
- Frontiers in Oncology; 9/23/2020, Vol. 10, pN.PAG-N.PAG, 10p
- Publication Year :
- 2020
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 2234943X
- Volume :
- 10
- Database :
- Complementary Index
- Journal :
- Frontiers in Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 146039347
- Full Text :
- https://doi.org/10.3389/fonc.2020.558339