EIF4E dysregulation drives simultaneous expression of B-cell lymphoma oncogenes. Homo sapiens

We demonstrate that eIF4E is active in lymphomas harboring multiple oncogene activation and drives simultaneous expression of oncogenes. As consequence, eIF4E inhibition decreased oncogene production and showed anti-lymphoma effect in “double-hit” and “triple-hit” lymphomas in vitro and in patient-derived xenografts. We identified the Hsp90 complex as a critical regulator of eIF4E activity in the nucleus as part of the nuclear export complex and in the cytosol as a part of active ribosomes. Hsp90 inhibition decreased the expression and translation of eIF4E mRNA targets and cooperated with ribavirin to maximally inhibit double- and triple-hit DLBCL growth in xenografts.