Inhibitory effects of SEL201 in acute myeloid leukemia
| Autor: | Mariafausta Fischietti, Aroop K. Kar, Frank Eckerdt, Leonidas C. Platanias, Elspeth M. Beauchamp, Alain Mina, Diana Saleiro, Elizabeth A. Eklund, Rebekah Siliezar, Krzysztof Brzózka, Ewa M. Kosciuczuk, Gavin T. Blyth, Sameem Abedin, Tomasz Rzymski |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway kinase inhibitor Kinase Chemistry Cell growth MNK EIF4E Myeloid leukemia acute myeloid leukemia SEL201 3. Good health 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Oncology Cell culture eIF4E hemic and lymphatic diseases 030220 oncology & carcinogenesis Cancer research Phosphorylation Protein kinase A Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.27388 |
| Popis: | MAPK interacting kinase (MNK), a downstream effector of mitogen-activated protein kinase (MAPK) pathways, activates eukaryotic translation initiation factor 4E (eIF4E) and plays a key role in the mRNA translation of mitogenic and antiapoptotic genes in acute myeloid leukemia (AML) cells. We examined the antileukemic properties of a novel MNK inhibitor, SEL201. Our studies provide evidence that SEL201 suppresses eIF4E phosphorylation on Ser209 in AML cell lines and in primary patient-derived AML cells. Such effects lead to growth inhibitory effects and leukemic cell apoptosis, as well as suppression of leukemic progenitor colony formation. Combination of SEL201 with 5’-azacytidine or rapamycin results in synergistic inhibition of AML cell growth. Collectively, these results suggest that SEL201 has significant antileukemic activity and further underscore the relevance of the MNK pathway in leukemogenesis. |
| Databáze: | OpenAIRE |
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