Expression of possible targets for new proteasome inhibitors in diffuse large B-cell lymphoma

Delforoush, Maryam,1980-Uppsala universitet,Experimentell och klinisk onkologi,Gunilla Enblad (author)

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.

Berglund, MattiasKarolinska Institutet,Uppsala universitet,Experimentell och klinisk onkologi(Swepub:uu)mattiber (author)
Edqvist, Per-HenrikUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)peedq227 (author)
Sundström, ChristerUppsala universitet,Experimentell och klinisk onkologi(Swepub:uu)chrisund (author)
Gullbo, JoachimUppsala universitet,Experimentell och klinisk onkologi(Swepub:uu)joacgull (author)
Enblad, GunillaUppsala universitet,Experimentell och klinisk onkologi(Swepub:uu)gunienbl (author)
Uppsala universitetExperimentell och klinisk onkologi (creator_code:org_t)

By the author/editor: Delforoush, Mary ...; Berglund, Mattia ...; Edqvist, Per-Hen ...; Sundström, Chris ...; Gullbo, Joachim; Enblad, Gunilla

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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