Comparative Proteomic Profiling of Refractory/relapsed Multiple Myeloma Reveals Biomarkers Involved in Resistance to Bortezomib-based Therapy

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Aug 17

PMID 27527861

Citations 38

Authors

Dominik Dytfeld

Magdalena Luczak

Tomasz Wrobel

Lidia Usnarska-Zubkiewicz

Katarzyna Brzezniakiewicz

Krzysztof Jamroziak

Krzysztof Giannopoulos

Anna Przybylowicz-Chalecka

Blazej Ratajczak

Joanna Czerwinska-Rybak

Adam Nowicki

Monika Joks

Elzbieta Czechowska

Magdalena Zawartko

Tomasz Szczepaniak

Norbert Grzasko

Marta Morawska

Maciej Bochenek

Tadeusz Kubicki

Michalina Morawska

Katarzyna Tusznio

Andrzej Jakubowiak

MieczysA Aw Komarnicki

Affiliations

Soon will be listed here.

Abstract

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.

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