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Expression of possible targets for new proteasome inhibitors in diffuse large B-cell lymphoma
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. (Gunilla Enblad)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
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2017 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 98, no 1, 52-56 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: Investigating expression of possible targets for proteasome inhibitors in patients with diffuse large B-cell lymphoma (DLBCL) and correlating the findings to clinical parameters and outcome.

Methods: Tumour material from 92 patients with DLBCL treated with either R-CHOP like (n = 69) or CHOP like (n = 23) regimens were stained for possible targets of proteasome inhibitors.

Results: The primary target molecule of bortezomib, proteasome subunit beta, type 5 (PSMB5), was not detected in the tumour cells in any of the cases but showed an abundant expression in cells in the microenvironment. However, the deubiquitinases (DUBs) of the proteasome, the ubiquitin carboxyl-terminal hydrolase L5 (UCHL5) and the ubiquitin specific peptidase 14 (USP14), were detected in the cytoplasm of the tumour cells in 77% and 74% of the cases, respectively. The adhesion regulating molecule 1 (ADRM1) was detected in 98% of the cases. There was no correlation between the expression of any of the studied markers and clinical outcome or GC/non-GC phenotype.

Conclusions: We suggest that UCHL5 and/or USP14 should be further evaluated as new targets for proteasome inhibitors in DLBCL. The lack of expression of PSMB5 on the tumour cells might provide an explanation of the relatively poor results of bortezomib in DLBCL.

Place, publisher, year, edition, pages
2017. Vol. 98, no 1, 52-56 p.
Keyword [en]
proteasome inhibitors, UCHL5, USP14
National Category
Medical and Health Sciences Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-280542DOI: 10.1111/ejh.12784ISI: 000393166600008PubMedID: 27301795OAI: oai:DiVA.org:uu-280542DiVA: diva2:911147
Funder
Swedish Cancer Society
Available from: 2016-03-11 Created: 2016-03-11 Last updated: 2017-11-30Bibliographically approved

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Delforoush, MaryamBerglund, MattiasEdqvist, Per-HenrikGullbo, JoachimEnblad, Gunilla

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Delforoush, MaryamBerglund, MattiasEdqvist, Per-HenrikSundström, ChristerGullbo, JoachimEnblad, Gunilla
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Experimental and Clinical OncologyDepartment of Immunology, Genetics and PathologyScience for Life Laboratory, SciLifeLab
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European Journal of Haematology
Medical and Health SciencesCancer and Oncology

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