(Immuno)proteasomes as therapeutic target in acute leukemia

Jacqueline Cloos, Margot S.F. Roeten, Niels E. Franke, Johan van Meerloo, Sonja Zweegman, Gertjan J.L. Kaspers, Gerrit Jansen

Research output: Contribution to journalArticleAcademicpeer-review

26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1-17
Number of pages17
JournalCancer and Metastasis Reviews
DOIs
Publication statusPublished - Dec 2017

Keywords

  • Constitutive proteasome
  • Drug resistance
  • Immunoproteasome
  • Leukemia
  • Proteasome inhibition

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