Inhibitory effects of SEL201 in acute myeloid leukemia

Ewa M. Kosciuczuk, Aroop K. Kar, Gavin T. Blyth, Mariafausta Fischietti, Sameem Abedin, Alain A. Mina, Rebekah Siliezar, Tomasz Rzymski, Krzysztof Brzozka, Elizabeth A. Eklund, Elspeth M. Beauchamp, Frank Eckerdt, Diana Saleiro, Leonidas C. Platanias*

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Scopus 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.

Original languageEnglish (US)
Pages (from-to)7112-7121
Number of pages10
JournalOncotarget
Volume10
Issue number67
StatePublished - Jan 1 2019

Keywords

  • Acute myeloid leukemia
  • EIF4E
  • Kinase inhibitor
  • MNK
  • SEL201

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Kosciuczuk, E. M., Kar, A. K., Blyth, G. T., Fischietti, M., Abedin, S., Mina, A. A., Siliezar, R., Rzymski, T., Brzozka, K., Eklund, E. A., Beauchamp, E. M., Eckerdt, F., Saleiro, D., & Platanias, L. C. (2019). Inhibitory effects of SEL201 in acute myeloid leukemia. Oncotarget, 10(67), 7112-7121.