(Immuno)proteasomes as therapeutic target in acute leukemia

Cancer Metastasis Rev. 2017 Dec;36(4):599-615. doi: 10.1007/s10555-017-9699-4.


The clinical efficacy of proteasome inhibitors in the treatment of multiple myeloma has encouraged application of proteasome inhibitor containing therapeutic interventions in (pediatric) acute leukemia. Here, we summarize the positioning of bortezomib, as first-generation proteasome inhibitor, and second-generation proteasome inhibitors in leukemia treatment from a preclinical and clinical perspective. Potential markers for proteasome inhibitor sensitivity and/or resistance emerging from leukemia cell line models and clinical sample studies will be discussed focusing on the role of immunoproteasome and constitutive proteasome (subunit) expression, PSMB5 mutations, and alternative mechanisms of overcoming proteolytic stress.

Keywords: Constitutive proteasome; Drug resistance; Immunoproteasome; Leukemia; Proteasome inhibition.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Bortezomib / administration & dosage
  • Bortezomib / pharmacology*
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm
  • Humans
  • Leukemia / drug therapy*
  • Leukemia / enzymology*
  • Leukemia / genetics
  • Leukemia / immunology
  • Molecular Targeted Therapy
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / immunology
  • Proteasome Endopeptidase Complex / metabolism
  • Proteasome Inhibitors / administration & dosage
  • Proteasome Inhibitors / pharmacology*


  • Proteasome Inhibitors
  • Bortezomib
  • PSMB5 protein, human
  • Proteasome Endopeptidase Complex