Most cited article - PubMed ID 24958999
Proteome changes in the plasma of myelodysplastic syndrome patients with refractory anemia with excess blasts subtype 2
- Keywords
- Myelodysplastic syndrome, Plasma proteome, Proteomics,
- MeSH
- Humans MeSH
- Myelodysplastic Syndromes * diagnosis MeSH
- Proteomics * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
In recent years the plasma proteomes of several different myelodysplastic syndrome (MDS) subgroups have been investigated and compared with those of healthy donors. However, the resulting data do not facilitate a direct and statistical comparison of the changes among the different MDS subgroups that would be useful for the selection and proposal of diagnostic biomarker candidates. The aim of this work was to identify plasma protein biomarker candidates for different MDS subgroups by reanalyzing the proteomic data of four MDS subgroups: refractory cytopenia with multilineage dysplasia (RCMD), refractory anemia or refractory anemia with ringed sideroblasts (RA-RARS), refractory anemia with excess blasts subtype 1 (RAEB-1), and refractory anemia with excess blasts subtype 2 (RAEB-2). Reanalysis of a total of 47 MDS patients revealed biomarker candidates, with alpha-2-HS-glycoprotein and leucine-rich alpha-2-glycoprotein as the most promising candidates.
- MeSH
- Biomarkers blood MeSH
- Adult MeSH
- alpha-2-HS-Glycoprotein metabolism MeSH
- Glycoproteins blood MeSH
- Middle Aged MeSH
- Humans MeSH
- Myelodysplastic Syndromes blood MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- AHSG protein, human MeSH Browser
- Biomarkers MeSH
- alpha-2-HS-Glycoprotein MeSH
- Glycoproteins MeSH
- LRG1 protein, human MeSH Browser
Our aim was to search for proteome changes in peripheral blood mononuclear cells (PBMCs) of MDS patients with refractory cytopenia with multilineage dysplasia. PBMCs were isolated from a total of 12 blood samples using a Histopaque-1077 solution. The proteins were fractioned, separated by 2D SDS-PAGE (pI 4-7), and double-stained. The proteomes were compared and statistically processed with Progenesis SameSpots; then proteins were identified by nano-LC-MS/MS. Protein functional association and expression profiles were analyzed using the EnrichNet application and Progenesis SameSpots hierarchical clustering software, respectively. By comparing the cytosolic, membrane, and nuclear fractions of the two groups, 178 significantly (P < 0.05, ANOVA) differing spots were found, corresponding to 139 unique proteins. Data mining of the Reactome and KEGG databases using EnrichNet highlighted the possible involvement of the identified protein alterations in apoptosis, proteasome protein degradation, heat shock protein action, and signal transduction. Western blot analysis revealed underexpression of vinculin and advanced fragmentation of fermitin-3 in MDS patients. To the best of our knowledge, this is the first time that proteome changes have been identified in the mononuclear cells of MDS patients. Vinculin and fermitin-3, the proteins involved in cell adhesion and integrin signaling, have been shown to be dysregulated in MDS.
- MeSH
- Databases, Protein * MeSH
- Adult MeSH
- Leukocytes, Mononuclear metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Myelodysplastic Syndromes metabolism MeSH
- Pilot Projects MeSH
- Proteome metabolism MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Proteome MeSH