Departament de Ciències Fisiològiques, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona-IDIBELL (Institut d'Investigació Biomèdica de Bellvitge), L'Hospitalet de Llobregat, Barcelona, Spain.
Servei d'Hematologia Clínica, Institut Català d'Oncologia (ICO)-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
Haematologica. 2017 Sep;102(9):1587-1593. doi: 10.3324/haematol.2016.162958. Epub 2017 Jun 15.
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.
氟利嗪啉是一种新的合成分子，通过选择性靶向抑制蛋白诱导细胞凋亡。在本研究中，评估了氟利嗪啉在 34 例慢性淋巴细胞白血病患者的原发性样本中的促凋亡作用。氟利嗪啉在低微摩尔浓度范围内诱导慢性淋巴细胞白血病细胞凋亡。所有原发性样本均对氟利嗪啉敏感，与患者的临床或遗传特征无关，而正常 T 淋巴细胞则不那么敏感。氟利嗪啉增加了慢性淋巴细胞白血病细胞中促凋亡 B 细胞淋巴瘤 2 家族成员 NOXA 的蛋白水平。此外，氟利嗪啉与伊布替尼、5-氨基咪唑-4-甲酰胺核苷或 venetoclax 协同诱导细胞凋亡。这些结果表明，靶向抑制蛋白可能是慢性淋巴细胞白血病的一种新的治疗策略。
