Title:A Bottom-Up Proteomic Approach in Bone Marrow Plasma Cells of Newly Diagnosed Multiple Myeloma Patients
Volume: 18
Issue: 5
Author(s): Beycan Ayhan, Seçil Karahisar Turan, N. Pınar Barkan, Klara Dalva, Meral Beksaç and Duygu Özel Demiralp*
Affiliation:
- Biomedical Engineering Department, Faculty of Engineering, Ankara University, Ankara,Turkey
Keywords:
Bone marrow, multiple myeloma, plasma cells, 2-D gel electrophoresis, matrix-assisted laser desorption-ionization
mass spectrometry, peptide mass fingerprinting.
Abstract:
Background: Multiple myeloma (MM) is characterized by infiltration of bone marrow
(BM) with clonal malignant plasma cells. The percentage of plasma cells in the BM is required for
both diagnosis and prognosis.
Objective: Intracellular protein screening and quantitative proteomic analysis were performed in
myeloma plasma cells with an aim to compare expressions between low (0-9%), intermediate
(10-20%) and high (>20%) plasma cell infiltration groups.
Methods: BM aspiration samples were collected from newly diagnosed untreated patients with
MM. The samples were pooled into three groups according to the plasma cell content (PCC) in the
BM: group 1 (0-9%), group 2 (10-20%) and group 3 (>20%). Protein profiles were obtained and
proteins were identified by peptide mass fingerprinting analysis.
Results: Differentially expressed proteins were detected between all groups. The identified proteins
are Endoplasmin, Calreticulin, Protein Disulfide-isomerase, Marginal zone B and B1 cell specific
protein/pERp1, Actin cytoplasmic 1, Myeloblastin, Thioredoxin domain-containing protein 5,
Ig kappa chain C region, Apoptosis regulator B-cell lymphoma 2 and Peroxiredoxin-4.
Conclusion: Proteins involved in cell proliferation, apoptosis, redox homeostasis and unfolded protein
disposal through endoplasmic reticulum-associated degradation machinery have been found to
be correlated to PCC. Our results confirm earlier reports regarding the potential effects of identified
proteins in the major signaling pathways that lead to cancer. Moreover, this study reveals a
novel association between PCC levels and MM. It further highlights the roles of Marginal zone B
and B1 cell specific proteins in MM, which could be used as candidate biomarkers in future
studies.