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

  • Patricia M.A. Zehnle
    Affiliations
    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
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  • Author Footnotes
    1 Present address: Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
    Ying Wu
    Footnotes
    1 Present address: Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
    Affiliations
    Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University Medical Center of Freiburg, Freiburg, Germany
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  • Henrike Pommerening
    Affiliations
    Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University Medical Center of Freiburg, Freiburg, Germany
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  • Miriam Erlacher
    Correspondence
    Offprint requests to Miriam Erlacher, Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University Medical Center of Freiburg, Mathildenstrasse 1, 79106 Freiburg, Germany
    Affiliations
    Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University Medical Center of Freiburg, Freiburg, Germany
    Search for articles by this author
  • Author Footnotes
    1 Present address: Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

      Highlights

      • 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.
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