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.
