Inhibitory effects of SEL201 in acute myeloid leukemia

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...

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Detalles Bibliográficos
Autores principales: Kosciuczuk, Ewa M., Kar, Aroop K., Blyth, Gavin T., Fischietti, Mariafausta, Abedin, Sameem, Mina, Alain A., Siliezar, Rebekah, Rzymski, Tomasz, Brzozka, Krzysztof, Eklund, Elizabeth A., Beauchamp, Elspeth M., Eckerdt, Frank, Saleiro, Diana, Platanias, Leonidas C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2019
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935253/
https://www.ncbi.nlm.nih.gov/pubmed/31903169
http://dx.doi.org/10.18632/oncotarget.27388
Descripción
Sumario: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.

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