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.
Primary breast lymphoma (PBL) is a rare disease accounting for 0.4-0.5% of all breast malignancies. Diffuse large B-cell lymphoma (DLBCL) is the most common histological diagnosis. The clinical presentation of PBLs is usually no different from that of carcinoma. In this paper we review the literature on the clinical presentation, diagnosis, prognostic factors and treatment options of PBL. In the light of the information gained we discuss three patients with primary breast lymphoma (one with a central nervous system relapse) who were treated in our department in the years 2002-2007. In conclusion: there is no consensus on the question of how to best treat PBL: chemotherapy, radiotherapy or combined therapy. However, the last approach to be the most successful one. Due to high incidence of central nervous system (CNS) involvement in PBL patients, many authors strongly believe that patients with aggressive forms of PBL should receive CNS infiltration prophylaxis, even in the early stages, as this may improve the outcome and significantly reduce the risk of a CNS disease relapse.
We compared the outcomes of multiple myeloma (MM) patients aged 21-40 and 41-60 years in the novel agent era. This case-control study included 1089 patients between 2000 and 2015. Cases and controls were matched for sex, International Staging System (ISS) stage and institution. There were 173 patients in the younger group and 916 patients in the older group. Younger patients presented with a higher incidence of lytic lesions (82% vs. 72%; P = 0·04) and high-risk cytogenetic abnormalities (83% vs. 68%; P = 0·007), but lower rate of elevated lactate dehydrogenase (21% vs. 44%; P < 0·001). Five- and 10-year overall survival (OS) in younger versus older patients was 83% vs. 67% and 56% vs. 39%, respectively (P < 0·001). Similar results were seen when studying the subset of 780 patients who underwent autologous transplantation. Younger patients with ISS stage 1 had a better OS than older patients (P < 0·001). There was no survival difference between younger and older patients with ISS stage 2 or 3. Younger MM patients, aged 21-40 years, treated in the era of novel agents have a better OS than their counterparts aged 41-60 years, but the survival advantage observed in younger patients was lost in more advanced stages of MM.
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