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Expression of ribosomal and actin network proteins and immunochemotherapy resistance in diffuse large B cell lymphoma patients

Artikel i vetenskaplig tidskrift
Författare Susanne Bram Ednersson
Martin Stenson
Mimmi Stern
G. Enblad
Henrik Fagman
Herman Nilsson-Ehle
Sverker Hasselblom
Per-Ola Andersson
Publicerad i British Journal of Haematology
Volym 181
Nummer/häfte 6
Sidor 770-781
ISSN 0007-1048
Publiceringsår 2018
Publicerad vid Institutionen för biomedicin, avdelningen för patologi
Institutionen för medicin
Sidor 770-781
Språk en
Länkar https://doi.org/10.1111/bjh.15259
Ämnesord DLBCL, proteomics, immunochemotherapy resistance, ribosomal, actin, rna-polymerase-i, cancer cells, cytoskeletal alterations, therapeutic, strategy, multiple-myeloma, drug-resistance, gastric-cancer, rho, gtpases, doxorubicin, proliferation, Hematology
Ämneskategorier Hematologi

Sammanfattning

Diffuse large B cell lymphoma (DLBCL) patients with early relapse or refractory disease have a very poor outcome. Immunochemotherapy resistance will probably, also in the era of targeted drugs, remain the major cause of treatment failure. We used proteomic mass spectrometry to analyse the global protein expression of micro-dissected formalin-fixed paraffin-embedded tumour tissues from 97 DLBCL patients: 44 with primary refractory disease or relapse within 1year from diagnosis (REF/REL), and 53 who were progression-free more than 5years after diagnosis (CURED). We identified 2127 proteins: 442 were found in all patients and 102 were differentially expressed. Sixty-five proteins were overexpressed in REF/REL patients, of which 46 were ribosomal proteins (RPs) compared with 2 of the 37 overexpressed proteins in CURED patients (P=76x10(-10)). Twenty of 37 overexpressed proteins in CURED patients were associated with actin regulation, compared with 1 of 65 in REF/REL patients (P=14x10(-9)). Immunohistochemical staining showed higher expression of RPS5 and RPL17 in REF/REL patients while MARCKS-like protein, belonging to the actin network, was more highly expressed in CURED patients. Even though functional studies aimed at individual proteins and protein interactions to evaluate potential clinical effect are needed, our findings suggest new mechanisms behind immunochemotherapy resistance in DLBCL.

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