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

Barbara Dapas, Gabriele Pozzato, Sonia Zorzet, Sara Capolla, Macor Paolo, Bruna Scaggiante, Michela Coan, Chiara Guerra, Chiara Gnan, Valter Gattei, Fabrizio Zanconati, Gabriele Grassi

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)118895
Number of pages11
JournalInternational Journal of Pharmaceutics
Volume574
DOIs
Publication statusPublished - Jan 25 2020

Keywords

  • Aptamer
  • Chronic lymphocytic leukemia
  • Eukaryotic elongation factor 1A1 protein
  • siRNA

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