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The molecular heterogeneity of acute myeloid leukemia (AML) underlies the wide variation in responses to standard therapy. This heterogeneity occurs at multiple regulatory steps affecting cell survival and proliferation.1 We identified overexpression of the eukaryotic translation initiation factor 4E (eIF4E) as a targetable aberrancy in all examined cases of M4 and M5 FAB (French, American and British classification) AML subtypes, as well as in some M0, M1, and M2 subtypes.2 eIF4E is both over-expressed and highly enriched in the nucleus of these specimens. eIF4E acts in nuclear mRNA export and translation of specific transcripts necessary for the promotion of proliferation, survival and metastases.3,4 These eIF4E functions depend on its binding the m7G cap on the 5′ end of mRNAs.3,4 Use of ribavirin, a competitive inhibitor of the m7G cap, impairs the biochemical and oncogenic functions of eIF4E.5,6 The first clinical trial to directly target eIF4E activity used ribavirin in AML patients with elevated eIF4E who were unfit for induction chemotherapy or who had relapsed disease.7 Complete and partial responses were observed, and responding patients demonstrated a reduction in overall levels of eIF4E, loss of its nuclear localization, and impaired production of eIF4E targets.7

A phase I trial of ribavirin and low-dose cytarabine for the treatment of relapsed and refractory acute myeloid leukemia with elevated eIF4E