Inhibition of prohibitins and translation in chronic lymphocytic leukemi

Project Details


Translation is a physiological process frequently disregulated in cancer cellsin which the synthesis of proteins is globally increased or switched towardsthe specific synthesis of certain oncogenic proteins. In chronic lymphocyticleukemia (CLL), translation initiation complexes (eIF4) are most oftenoveractivated following BCR involvement and abnormal kinase activity(LYN, SYK and BTK); thus leading to increased translation of MYC.The purpose of this research project is to investigate the therapeuticefficacy and mode of action of 2 new molecules (FL3 and fluorizoline) toinhibit translation machinery and prohibitins in chronic lymphocytic leukemia(CLL), both in patient cells and in a murine model. Prohibitins arechaperone proteins that can be localized at the plasma membrane, in thecytosol or in the mitochondrial membrane. These proteins orchestrate manycellular functions such as transcription, metabolism, cytoskeletalreorganization and cell survival. In cancer cells, these proteins are alsoinvolved in the regulation of the Ras / Raf / ERK pathway which activatesthe eiF4F translation initiation complex. This project also aims to decipherby biochemical and molecular methods the cellular signaling pathwaysactivated by these two molecules, alone or in combination with the BTKinhibitor ibrutinib. We will also characterize by mass cytometry the tumor
microenvironment of mice treated with ibrutinib and FL3 or fluorizolin.
Effective start/end date1/10/1731/01/22


  • FNRS - Fonds National de la Recherche Scientifique: €187,200.00
  • FNRS - Fonds National de la Recherche Scientifique: €167,187.00


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