Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University Medical Center of Freiburg, Freiburg, Germany; Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, University Medical Center of Freiburg, Freiburg, Germany.
Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University Medical Center of Freiburg, Freiburg, Germany.
Exp Hematol. 2022 Jun;110:1-12. doi: 10.1016/j.exphem.2022.03.006. Epub 2022 Mar 18.
BH3 mimetics constitute a novel concept of antitumor therapy, inducing apoptosis via inhibition of pro-survival BCL-2 proteins. Programmed cell death is fundamental for physiological hematopoiesis; hence hematological side effects of these compounds are conceivable. Navitoclax and venetoclax have been studied extensively in the clinical setting; our knowledge of the more recently developed BCL-2 protein inhibitors specifically targeting MCL-1 or BCL-X, however, is restricted mainly to preclinical experiments. To delineate possible adverse effects of novel BH3 mimetics on the human hematopoietic system, this review summarizes current knowledge of the function of specific antiapoptotic BCL-2 proteins in physiological hematopoiesis.
BH3 拟似物构成了一种通过抑制抗凋亡 BCL-2 蛋白来诱导细胞凋亡的新型抗肿瘤治疗方法。程序性细胞死亡对于生理造血至关重要；因此可以想象这些化合物会产生血液学副作用。纳维托昔单抗和维奈托克已在临床环境中进行了广泛研究；然而，我们对专门针对 MCL-1 或 BCL-X 的新型 BCL-2 蛋白抑制剂的了解主要局限于临床前实验。为了阐明新型 BH3 拟似物对人类造血系统可能产生的不良影响，本综述总结了特定抗凋亡 BCL-2 蛋白在生理造血中的功能的现有知识。
