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25-10-2017 | Acute leukemia | Article

(Immuno)proteasomes as therapeutic target in acute leukemia

Journal:
Cancer and Metastasis Reviews

Authors: Jacqueline Cloos, Margot SF Roeten, Niels E Franke, Johan van Meerloo, Sonja Zweegman, Gertjan JL Kaspers, Gerrit Jansen

Publisher: Springer US

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.

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