Abstract
While multiple myeloma (MM) treatment with proteasome inhibitors and other agents yields encouraging results, primary and secondary resistance remains an emerging problem. An important factor in such treatment resistance is the overexpression of several proteins. The present study comprehensively evaluates the expression of POMP, PSMB5, NRF2, XBP1, cMAF and MAFb proteins in plasma cells isolated from the bone marrow of 39 MM patients treated with bortezomib-based regimens using an enzyme-linked immunosorbent assay (ELISA). The proteins were selected on the basis of previous laboratory and clinical studies in bortezomib-treated MM patients. It was found that the expression of the investigated proteins did not significantly differ between bortezomib-sensitive and bortezomib-refractory patients. However, the expression of some proteins correlated with overall survival (OS); this was significantly shorter in patients with higher POMP expression (HR 2.8, 95% CI: 1.1–7.0, p = 0.0277) and longer in those with higher MAFB expression (HR 0.32, 95% CI: 0.13–0.80, p = 0.0147). Our results indicate that a high expression of POMP and MAFB in MM plasma cells may serve as predictors of OS in MM patients treated with bortezomib-based regimens. However, further studies are needed to determine the role of these factors in effective strategies for improving anti-myeloma therapy.
Highlights
The present study examined the levels of six proteins (POMP, proteasome subunit β5 (PSMB5), Nuclear factor erythroid 2-related factor 2 (NRF2), XBP1, cMAF and MAFB) in the plasma cells (PC) from bone marrow (BM) of 39 MM patients, treated with bortezomib-based regimens
Patients exhibited lower sXBP1 levels [24]. These observations suggest that determination of sXBP1 levels prior to bortezomib treatment in MM may be useful to predict bortezomib resistance; these results were not confirmed in our present study
The results demonstrate that a proteomics-based approach using a combination of immunodepletion, 2D-difference gel electrophoresis analysis, mass spectrometry and enzyme-linked immunosorbent assay (ELISA) is an effective strategy for identifying proteins useful for predicting response to thalidomide
Summary
Proteasome inhibitors act via various mechanisms, including by exerting direct effects on myeloma cells, and inhibiting the activity of cytokines as well as several adhesion molecules and angiogenesis They are known to inhibit the action of nuclear factor kappa B (NF-κB), which plays a key role in the survival and proliferation of MM cells. The proteins were selected on the basis of previous laboratory and clinical studies investigating their expression in bortezomib-sensitive and refractory MM patients and their influence on the treatment results of bortezomib-based regimens.
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