(Immuno)proteasomes as therapeutic target in acute leukemia

Cancer Metastasis Reviews
J CloosG Jansen

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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Methods Mentioned

BETA
xenograft
MDS

Clinical Trials Mentioned

NCT00873093
NCT01950611
NCT02112916
NCT02518750
NCT02553460
NCT02535806
NCT00410423
NCT00651781
NCT01534260
NCT01075425

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