Maryam Delforoush1, Mattias Berglund1, Per-Henrik Edqvist2, Christer Sundström1, Joachim Gullbo1,3, Gunilla Enblad1. 1. Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden. 2. Pathology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden. 3. Department of Medical Sciences, Section of Clinical Pharmacology, Uppsala University Hospital, Uppsala, Sweden.
Abstract
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.
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.
Authors: Yang Yu; Yanling Zhao; Yihui Fan; Zhenghu Chen; Hui Li; Jiaxiong Lu; Kevin Guo; Sarah E Woodfield; Sanjeev A Vasudevan; Jianhua Yang; Jed G Nuchtern Journal: Mol Cancer Ther Date: 2019-04-08 Impact factor: 6.261
Authors: Ana Sofia Carvalho; Henrique Baeta; Andreia F A Henriques; Mostafa Ejtehadifar; Erin M Tranfield; Ana Laura Sousa; Ana Farinho; Bruno Costa Silva; José Cabeçadas; Paula Gameiro; Maria Gomes da Silva; Hans Christian Beck; Rune Matthiesen Journal: Int J Mol Sci Date: 2021-10-12 Impact factor: 5.923