Targeting of phospho-eIF4E by homoharringtonine eradicates a distinct subset of human acute myeloid leukemia

Abstract

More than half of the patients with acute myeloid leukemia (AML) fail to achieve long-term disease-free survival with current therapies and novel therapeutic strategies are urgently needed. The effects of homoharringtonine (HHT) on the growth of AML cell lines and primary leukemia cells were examined using MTT, colony formation assay. The effects of HHT on both eukaryotic translation initiation factor 4E (eIF4E) and phospho-eIF4E(p-eIF4E) were examined through western blot and immunofluorescence staining. HHT selectively reduced levels of p-eIF4E and its downstream oncoprotein Mcl-1, and potently inhibited in vitro and in vivo the growth of a distinct subset of AML cells and primary leukemia cells expressing high level of p-eIF4E through apoptosis. Our findings suggest that HHT might be a first-in-class p-eIF4E-targeted drug and offer a novel therapeutic option for AML patients expressing high level of p-eIF4E.

Keywords:

• Phospho-eIF4E
• homoharringtonine
• acute myeloid leukemia

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2017.1390229.

Additional information

Funding

This work was supported in part by Natural Science Foundation of China [81600129] and Science and technology Project of Hangzhou [2016Z01].