The prohibitin-binding compound fluorizoline induces apoptosis in chronic lymphocytic leukemia cells ex vivo but fails to prevent leukemia development in a murine model.
- Tumor Stroma Interactions
Chronic lymphocytic leukemia (CLL), the most frequent leukemia in adults, is characterized by an accumulation of monoclonal B cells with a mature phenotype in the blood and lymphoid organs. Despite considerable advances in the treatment of patients, CLL remains an incurable disorder and therefore, novel therapies are needed. New compounds harboring a trifluorinated thiazoline scaffold have been recently described for their pro-apoptotic properties. Indeed, a diaryl trifluorothiazoline, named fluorizoline, demonstrated a high apoptosis induction in different cancer cells in vitro by binding to prohibitin (PHB) 1 and 2. Very recently, fluorizoline was reported to efficiently induce apoptosis in CLL cells derived from patients, showing synergistic effects with other drugs used in CLL treatment such as the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib. However, no assessment of fluorizoline efficacy in vivo was reported by all these studies. Here, we confirmed that fluorizoline strongly induces apoptosis in primary CLL cells through the induction of NOXA. However, we also demonstrated that fluorizoline, contrary to ibrutinib, fails to control CLL development in a relevant mouse model of aggressive disease.