(Immuno)proteasomes as therapeutic target in acute leukemia

Jacqueline Cloos; Margot Sf Roeten; Niels E. Franke; Johan van Meerloo; Sonja Zweegman; Gertjan Jl Kaspers; Gerrit Jansen

doi:10.1007/s10555-017-9699-4

(Immuno)proteasomes as therapeutic target in acute leukemia

Jacqueline Cloos, Margot Sf Roeten, Niels E. Franke, Johan van Meerloo, Sonja Zweegman, Gertjan Jl Kaspers, Gerrit Jansen

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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 language	English
Pages (from-to)	599-615
Number of pages	17
Journal	Cancer and Metastasis Reviews
Volume	36
Issue number	4
DOIs	https://doi.org/10.1007/s10555-017-9699-4
Publication status	Published - 1 Dec 2017

Keywords

Constitutive proteasome
Drug resistance
Immunoproteasome
Leukemia
Proteasome inhibition

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title = "(Immuno)proteasomes as therapeutic target in acute leukemia",

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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AU - Cloos, Jacqueline

AU - Roeten, Margot Sf

AU - Franke, Niels E.

AU - van Meerloo, Johan

AU - Zweegman, Sonja

AU - Kaspers, Gertjan Jl

AU - Jansen, Gerrit

PY - 2017/12/1

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N2 - 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.

AB - 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.

KW - Constitutive proteasome

KW - Drug resistance

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KW - Leukemia

KW - Proteasome inhibition

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(Immuno)proteasomes as therapeutic target in acute leukemia

Abstract

Keywords

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