Plasma proteome changes associated with refractory cytopenia with multilineage dysplasia

Májek Pavel, Reicheltová Zuzana, Suttnar Jiå™Í, Äœermák Jaroslav, Dyr

Description

Refractory cytopenia with multilineage dysplasia (RCMD) is a subgroup of myelodysplastic syndrome (MDS), which belongs to oncohematological diseases, occurring particularly in elderly patients, and represents a heterogeneous group of bone marrow diseases. The goal of this study was to look for plasma proteins that changed quantitatively or qualitatively in RCMD patients. Results A total of 46 plasma samples were depleted, proteins were separated by 2D SDS-PAGE (pI 4-7), and proteomes were compared using Progenesis SameSpots statistical software. Proteins were identified by nanoLC-MS/MS. Sixty-one unique, significantly (p < 0.05, ANOVA) different spots were found; proteins in 59 spots were successfully identified and corresponded to 57 different proteins. Protein fragmentation was observed in several proteins: complement C4-A, complement C4-B, inter-alpha-trypsin inhibitor heavy chain H4, and endorepellin. Conclusions This study describes proteins, which change quantitatively or qualitatively in RCMD patients, and represents the first report on significant alterations in C4-A and C4-B complement proteins and ITIH4 fragments in patients with MDS-RCMD.

Sujets

• Myelodysplastic syndrome
• Dysplasia
• Protéome

Informations

• Publié par: biomed
• Publié le: 01 janvier 2011
• Nombre de lectures: 9
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

Májeket al.Proteome Science2011,9:64 http://www.proteomesci.com/content/9/1/64

R E S E A R C HOpen Access Plasma proteome changes associated with refractory cytopenia with multilineage dysplasia * Pavel Májek , Zuzana Reicheltová, Jiří Suttnar, JaroslavČermák and Jan E Dyr

Abstract Background:Refractory cytopenia with multilineage dysplasia (RCMD) is a subgroup of myelodysplastic syndrome (MDS), which belongs to oncohematological diseases, occurring particularly in elderly patients, and represents a heterogeneous group of bone marrow diseases. The goal of this study was to look for plasma proteins that changed quantitatively or qualitatively in RCMD patients. Results:A total of 46 plasma samples were depleted, proteins were separated by 2D SDSPAGE (pI 47), and proteomes were compared using Progenesis SameSpots statistical software. Proteins were identified by nanoLC MS/MS. Sixtyone unique, significantly (p < 0.05, ANOVA) different spots were found; proteins in 59 spots were successfully identified and corresponded to 57 different proteins. Protein fragmentation was observed in several proteins: complement C4A, complement C4B, interalphatrypsin inhibitor heavy chain H4, and endorepellin. Conclusions:This study describes proteins, which change quantitatively or qualitatively in RCMD patients, and represents the first report on significant alterations in C4A and C4B complement proteins and ITIH4 fragments in patients with MDSRCMD. Keywords:myelodysplastic syndrome, refractory cytopenia, dysplasia, proteome

Background Refractory cytopenia with multilineage dysplasia (RCMD) is a subgroup of myelodysplastic syndrome (MDS). MDS itself belongs to the group of oncohematological diseases, occurring particularly in elderly patients. It represents a heterogeneous group of bone marrow diseases character ized by blood cytopenias, ineffective hematopoiesis, and dysplasia in one or more blood cell lines. According to the WHO (World Health Organization) classification of MDS, RCMD is defined by the presence of bicytopenia or pancytopenia in peripheral blood and dysplastic changes that are present in 10% or more of the cells in two or more myeloid lineages in the bone marrow (with less than 15% ringed sideroblasts) [1]. Despite the efforts and development in MDS research within the last several years, the pathogenesis of MDS remains still unclear. Several studies have shown an up or downregulation of different groups of genes in MDS patients [26]; however, the results are in some cases

* Correspondence: [e-mail] Department of Biochemistry, Institute of Hematology and Blood Transfusion, Prague, Czech Republic

controversial and difficult to interpret. Proteomic tech niques might provide a new and more detailed set of information clarifying the molecular mechanisms involved in the development of MDS [7]. Complex pro teinprotein networks reflect the changes at the tran scription level, as well as changes induced by protein modifications depending on (patho) physiological condi tions in organisms. Posttranslational modifications of proteins including fragmentation or crosslinking are examples of changes detected exclusively by proteomic techniques [8], which may play a crucial role in the development and progression of the disease [9,10]. Twodimensional gel electrophoresis (especially 2D SDSPAGE) is one of the most widespread proteomic techniques. Despite some disadvantages like the coiden tification of proteins within a protein feature, a limited range of detection of lowabundant proteins, or pro blems with the analysis of basic and low molecular weight proteins, 2D electrophoresis offers both the pos sibilities to search for protein level changes and for pro tein posttranslational modifications. Differential proteome pattern analysis, based on either quantitative or qualitative changes, combined with the identification

© 2011 Májek et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.