Étudiant-chercheur étoile August 2014



Fadi Hariri

PhD student in Molecular Biology
Université de Montréal


Award-winning publication: The eukaryotic translation initiation factor eIF4E is a direct transcriptional target of NF-κB and is aberrantly regulated in acute myeloid leukemia

Published in: Leukemia, 2013; 27(10): 2047-55.
 

Abstract

"Leukemia comprises one third of childhood cancers, a quarter of which constitutes acute myeloid leukemias (AML). Children with M4/M5 AMLs are characterized by poor prognosis. Our group has previously demonstrated that the translation initiation factor eIF4E is elevated in M4/M5 AMLs; targeting eIF4E with ribavirin was correlated with clinical benefits in M4/M5 poor prognosis patients. Our lab has therefore set to understand the dysregulation of eIF4E in leukemia as well as other cancer subtypes such as lymphomas. In this paper I demonstrate the transcriptional regulation of the eIF4E gene by NF-kB, an oncogenic transcription factor highly active in AMLs, lymphomas and various cancers. Understanding the regulation of eIF4E will be of importance in the development of novel therapeutic regimens to target eIF4E gene expression and alleviate symptoms of poor prognosis AML patients as well as other cancers to further improve the efficacy of patient care."

As the oncogenes in question are highly involved in various cancers subtypes including acute myeloid leukemias (AML) and lymphomas, Fadi Hariri wanted to find a link between them in an attempt to develop efficient therapeutic solutions for targeting eIF4E in cancer in general and in leukemias and lymphomas in particular. Thus, he deciphered a mechanism that underlines eIF4E overexpression in AML, and he identified a differential regulation of this potent oncoprotein in specific subtypes of poor prognosis AML. The importance of this study lies in the development of novel therapeutic strategies to target eIF4E by combining ribavirin with specific NF-kB inhibitors that would more effectively target eIF4E, especially in the patients who eventually develop drug resistance.