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Inhibitory effects of SEL201 in acute myeloid leukemia. Oncotarget 2019 Dec 24;10(67):7112-7121

Date

01/07/2020

Pubmed ID

31903169

Pubmed Central ID

PMC6935253

DOI

10.18632/oncotarget.27388

Scopus ID

2-s2.0-85077552456   8 Citations

Abstract

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.

Author List

Kosciuczuk EM, Kar AK, Blyth GT, Fischietti M, Abedin S, Mina AA, Siliezar R, Rzymski T, Brzozka K, Eklund EA, Beauchamp EM, Eckerdt F, Saleiro D, Platanias LC

Author

Sameem Abedin MD Assistant Professor in the Medicine department at Medical College of Wisconsin