硼替佐米
蛋白酶体
淋巴瘤
弥漫性大B细胞淋巴瘤
癌症研究
表型
生物
切碎
蛋白酶体抑制剂
病理
医学
细胞生物学
免疫学
多发性骨髓瘤
基因
遗传学
作者
Maryam Delforoush,Mattias Berglund,Per‐Henrik Edqvist,Christer Sundström,Joachim Gullbo,Gunilla Enblad
摘要
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 ( PSMB 5), 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 ( DUB s) of the proteasome, the ubiquitin carboxyl‐terminal hydrolase L5 ( UCHL 5) and the ubiquitin specific peptidase 14 ( USP 14), were detected in the cytoplasm of the tumour cells in 77% and 74% of the cases, respectively. The adhesion regulating molecule 1 ( ADRM 1) 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 UCHL 5 and/or USP 14 should be further evaluated as new targets for proteasome inhibitors in DLBCL . The lack of expression of PSMB 5 on the tumour cells might provide an explanation of the relatively poor results of bortezomib in DLBCL .
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