Loading…

Comparative proteomic profiling of refractory/relapsed multiple myeloma reveals biomarkers involved in resistance to bortezomib-based therapy

Identifying biomarkers of the resistance in multiple myeloma (MM) is a key research challenge. We aimed to identify proteins that differentiate plasma cells in patients with refractory/relapsed MM (RRMM) who achieved at least very good partial response (VGPR) and in those with reduced response to PA...

Full description

Saved in:
Bibliographic Details
Published in:Oncotarget 2016-08, Vol.7 (35), p.56726-56736
Main Authors: Dytfeld, Dominik, Luczak, Magdalena, Wrobel, Tomasz, Usnarska-Zubkiewicz, Lidia, Brzezniakiewicz, Katarzyna, Jamroziak, Krzysztof, Giannopoulos, Krzysztof, Przybylowicz-Chalecka, Anna, Ratajczak, Blazej, Czerwinska-Rybak, Joanna, Nowicki, Adam, Joks, Monika, Czechowska, Elzbieta, Zawartko, Magdalena, Szczepaniak, Tomasz, Grzasko, Norbert, Morawska, Marta, Bochenek, Maciej, Kubicki, Tadeusz, Morawska, Michalina, Tusznio, Katarzyna, Jakubowiak, Andrzej, Komarnicki, MieczysÅ Aw
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Identifying biomarkers of the resistance in multiple myeloma (MM) is a key research challenge. We aimed to identify proteins that differentiate plasma cells in patients with refractory/relapsed MM (RRMM) who achieved at least very good partial response (VGPR) and in those with reduced response to PAD chemotherapy (bortezomib, doxorubicin and dexamethasone). Comparative proteomic analysis was conducted on pretreatment plasma cells from 77 proteasome inhibitor naïve patients treated subsequently with PAD due to RRMM. To increase data confidence we used two independent proteomic platforms: isobaric Tags for Relative and Absolute Quantitation (iTRAQ) and label free (LF). Proteins were considered as differentially expressed when their accumulation between groups differed by at least 50% in iTRAQ and LF. The proteomic signature revealed 118 proteins (35 up-regulated and 83 down-regulated in ≥ VGPR group). Proteins were classified into four classes: (1) involved in proteasome function; (2) involved in the response to oxidative stress; (3) related to defense response; and (4) regulating the apoptotic process. We confirmed the differential expression of proteasome activator complex subunit 1 (PSME1) by enzyme-linked immunosorbent assay. Increased expression of proteasomes and proteins involved in protection from oxidative stress (eg., TXN, TXNDC5) plays a major role in bortezomib resistance.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.11059