Effects of eEF1A1 targeting by aptamer/siRNA in chronic lymphocytic leukaemia cells.

ABSTRACT

BACKGROUND: The effectiveness of therapies for chronic lymphocytic leukemia (CLL), the most common leukemia in Western countries adults, can be improved via a deeper understanding of its molecular abnormalities. Whereas the isoforms of the eukaryotic elongation factor 1A (eEF1A1 and eEF1A2) are implicated in different tumors, no information are available in CLL. METHODS: eEF1A1/eEF1A2 amounts were quantitated in the lymphocytes of 46 CLL patients vs normal control (real time PCR, western blotting). eEF1A1 role in CLL was investigated in a cellular (MEC-1) and animal model of CLL via its targeting by an aptamer (GT75) or a siRNA (siA1) delivered by electroporation (in vitro) or lipofection (in vivo). RESULTS: eEF1A1/eEF1A2 were elevated in CLL lymphocytes vs control. eEF1A1 but not eEF1A2 levels were higher in patients which died during the study compared to those surviving. eEF1A1 targeting (GT75/siA1) resulted in MEC-1 viability reduction/autophagy stimulation and in vivo tumor growth down-regulation. CONCLUSIONS: The increase of eEF1A1 in dead vs surviving patients may confer to eEF1A1 the role of a prognostic marker for CLL and possibly of a therapeutic target, given its involvement in MEC-1 survival. Specific aptamer/siRNA released by optimized delivery systems may allow the development of novel therapeutic options.