Portal de Periódicos da CAPES

Stayin’ alive: BCL-2 proteins in the hematopoietic system

2022; Elsevier BV; Volume: 110; Linguagem: Inglês

10.1016/j.exphem.2022.03.006

1873-2399

Patricia M. A. Zehnle, Ying Wu, Henrike Pommerening, Miriam Erlacher,

Chronic Lymphocytic Leukemia Research

•Antiapoptotic BCL-2 proteins are essential to maintain the hematopoietic system. •BCL-2 protein dependency varies between the different blood cell lineages. •BH3 mimetics are novel anticancer drugs acting via inhibition of BCL-2 proteins. •Selective MCL-1 or BCL-XL inhibitors might cause severe hematological side effects. 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-XL, 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 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-XL, 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.