The prohibitin-binding compound fluorizoline induces apoptosis in chronic lymphocytic leukemia cells through the upregulation of NOXA and synergizes with ibrutinib, 5-aminoimidazole-4-carboxamide riboside or venetoclax
EHA Learning Center. Cosialls A. Sep 1, 2017; 196259
Topic: 3F Pediatric lymphoid malignancies
Ana M. Cosialls
Ana M. Cosialls
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Co-Authors: Helena Pomares, Daniel Iglesias-Serret, José Saura-Esteller, Sonia Núñez-Vázquez, Diana M. González-Gironès, Esmeralda de la Banda, Sara Preciado, Fernando Albericio, Rodolfo Lavilla, Gabriel Pons, Eva M. González-Barca, Joan Gil

Abstract: Fluorizoline is a new synthetic molecule that induces apoptosis by selectively targeting prohibitins. In the study herein, the pro-apoptotic effect of fluorizoline was assessed in 34 primary samples from patients with chronic lymphocytic leukemia. Fluorizoline induced apoptosis in chronic lymphocytic leukemia cells at concentrations in the low micromolar range. All primary samples were sensitive to fluorizoline irrespective of patients’ clinical or genetic features, whereas normal T lymphocytes were less sensitive. Fluorizoline increased the protein levels of the pro-apoptotic B-cell lymphoma 2 family member NOXA in chronic lymphocytic leukemia cells. Furthermore, fluorizoline synergized with ibrutinib, 5-aminoimidazole-4-carboxamide riboside or venetoclax to induce apoptosis. These results suggest that targeting prohibitins could be a new therapeutic strategy for chronic lymphocytic leukemia.

Article Number: 1587

Doi: 10.3324/haematol.2016.162958

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